806:
85:
4103:
859:
974:
404:
930:
1087:
718:
395:(such as SOS) recognizes the phosphorylated tyrosine on the receptor. This protein functions as a bridge which connects the RTK to an intermediate protein (such as GNRP), starting the intracellular signaling cascade. In turn, the intermediate protein stimulates GDP-bound Ras to the activated GTP-bound Ras. GAP eventually returns Ras to its inactive state. Activation of
706:
1026:
proliferation. Current research is focused on the action of the Wnt signaling pathway the regulation of stem cell choice to proliferate and self renew. This action of Wnt signaling in the possible control and maintenance of stem cells, may provide a possible treatment in cancers exhibiting aberrant Wnt signaling.
432:(formation of cells in blood). The Kit receptor and related tyrosine kinase receptors actually are inhibitory and effectively suppresses receptor firing. Mutant forms of the Kit receptor, which fire constitutively in a ligand-independent fashion, are found in a diverse array of cancerous malignancies.
448:
transcription is upregulated when Ras is in the GTP-bound state. The chemokines are then released from the cell, free to bind to another nearby cell. Paracrine signaling between neighboring cells creates this positive feedback loop. Thus, the constitutive transcription of upregulated proteins form
1025:
The Wnt signaling pathways are complex, involving many different elements, and therefore have many targets for misregulation. Mutations that cause constitutive activation of the Wnt signaling pathway lead to tumor formation and cancer. Aberrant activation of the Wnt pathway can lead to increase cell
2259:
Zsebo, Krisztina M.; Williams, David A.; Geissler, Edwin N.; Broudy, Virginia C.; Martin, Francis H.; Atkins, Harry L.; Hsu, Rou-Yin; Birkett, Neal C.; Okino, Kenneth H.; Murdock, Douglas C.; Jacobsen, Frederick W.; Langley, Keith E.; Smith, Kent A.; Takeish, Takashi; Cattanach, Bruce M.; Galli,
142:
Although the FGF family of paracrine factors has a broad range of functions, major findings support the idea that they primarily stimulate proliferation and differentiation. To fulfill many diverse functions, FGFs can be alternatively spliced or even have different initiation codons to create
1273:
Non-Smad signaling proteins contribute to the responses of the TGF-β pathway in three ways. First, non-Smad signaling pathways phosphorylate the Smads. Second, Smads directly signal to other pathways by communicating directly with other signaling proteins, such as kinases. Finally, the TGF-β
841:
orientation, cell polarity, cadherin mediated adhesion, and early development of embryos in many different organisms. Current research has indicated that deregulation of Wnt signaling plays a role in tumor formation, because at a cellular level, Wnt proteins often regulated
1082:
kinase activity. When a TGF-β superfamily ligand binds to the type II receptor, it recruits a type I receptor and activates it by phosphorylating the serine or threonine residues of its "GS" box. This forms an activation complex that can then phosphorylate SMAD proteins.
2346:
Melillo, Rosa Marina; Castellone, Maria
Domenica; Guarino, Valentina; De Falco, Valentina; Cirafici, Anna Maria; Salvatore, Giuliana; Caiazzo, Fiorina; Basolo, Fulvio; Giannini, Riccardo; Kruhoffer, Mogens; Orntoft, Torben; Fusco, Alfredo; Santoro, Massimo (2005).
632:. Paracrine signaling through the JAK-STAT pathway is necessary in the transition from stationary epithelial cells to mobile mesenchymal cells, which are capable of invading surrounding tissue. Only the JAK-STAT pathway has been found to induce migratory cells.
2661:
Shiang, Rita; Thompson, Leslie M.; Zhu, Ya-Zhen; Church, Deanna M.; Fielder, Thomas J.; Bocian, Maureen; Winokur, Sara T.; Wasmuth, John J. (1994). "Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia".
1013:
The Wnt signaling pathways are critical in cell-cell signaling during normal development and embryogenesis and required for maintenance of adult tissue, therefore it is not difficult to understand why disruption in Wnt signaling pathways can promote human
590:
The JAK-STAT signaling pathway is instrumental in the development of limbs, specifically in its ability to regulate bone growth through paracrine signaling of cytokines. However, mutations in this pathway have been implicated in severe forms of dwarfism:
399:
has the potential to initiate three signaling pathways downstream of Ras: Ras→Raf→MAP kinase pathway, PI3 kinase pathway, and Ral pathway. Each pathway leads to the activation of transcription factors which enter the nucleus to alter gene expression.
2625:
Bonaventure, J.; Rousseau, F.; Legeai-Mallet, L.; Le Merrer, M.; Munnich, A.; Maroteaux, P. (1996). "Common mutations in the fibroblast growth factor receptor 3 (FGFR3) gene account for achondroplasia, hypochondroplasia, and thanatophoric dwarfism".
1074:. There are five kinds of type II receptors and seven types of type I receptors in humans and other mammals. These receptors are known as "dual-specificity kinases" because their cytoplasmic kinase domain has weak tyrosine kinase activity but strong
100:
in the body - even between different species - are known to utilize a similar sets of paracrine factors in differential development. The highly conserved receptors and pathways can be organized into four major families based on similar structures:
965:. Active RhoA is able to induce cytoskeleton changes by activating Roh-associated kinase (ROCK) and affect gene transcription directly. Active Rac can directly induce cytoskeleton changes and affect gene transcription through activation of JNK.
789:. This connection between the Hedgehog signaling pathway and human cancers may provide for the possible of therapeutic intervention as treatment for such cancers. The Hedgehog signaling pathway is also involved in normal regulation of
894:, which is already working on DNA as a repressor, inhibiting the transcription of the genes it binds. Binding of β-catenin to Lef/Tcf works as a transcription activator, activating the transcription of the Wnt-responsive genes.
500:
After dimerization of the cytokine receptors following ligand binding, the JAKs transphosphorylate each other. The resulting phosphotyrosines attract STAT proteins. The STAT proteins dimerize and enter the nucleus to act as
745:(Ci), Fused, and Cos protein complex attached to microtubules to remain intact. In this conformation, the Ci protein is cleaved so that a portion of the protein is allowed to enter the nucleus and act as a transcriptional
379:
receptor. This conformational change activates the dormant kinase of each RTK on the tyrosine residue. Due to the fact that the receptor spans across the membrane from the extracellular environment, through the
1042:, secreted polypeptides that regulate development. Many developmental processes are under its control including gastrulation, axis symmetry of the body, organ morphogenesis, and tissue homeostasis in adults. All
611:
cell division is prematurely terminated, resulting in lethal dwarfism. Rib and limb bone growth plate cells are not transcribed. Thus, the inability of the rib cage to expand prevents the newborn's breathing.
129:
In order for paracrine factors to successfully induce a response in the receiving cell, that cell must have the appropriate receptors available on the cell membrane to receive the signals, also known as being
3492:
Neth, Peter; Ries, Christian; Karow, Marisa; Egea, Virginia; Ilmer, Matthias; Jochum, Marianne (2007). "The Wnt Signal
Transduction Pathway in Stem Cells and Cancer Cells: Influence on Cellular Invasion".
4154:
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of the
Hedgehog protein, which would be ligand dependent. In addition, therapy-induced Hedgehog pathway activation has been shown to be necessary for progression of Prostate Cancer tumors after
81:
environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.
644:
is involved in induction of cell types and the creation of tissue boundaries and patterning and are found in all bilateral organisms. Hedgehog proteins were first discovered and studied in
3747:
Wu, Jia-Wei; Hu, Min; Chai, Jijie; Seoane, Joan; Huse, Morgan; Li, Carey; Rigotti, Daniel J.; Kyin, Saw; Muir, Tom W.; Fairman, Robert; Massagué, Joan; Shi, Yigong (2001).
4117:
Betts, J Gordon; Desaix, Peter; Johnson, Eddie; Johnson, Jody E; Korol, Oksana; Kruse, Dean; Poe, Brandon; Wise, James; Womble, Mark D; Young, Kelly A (July 24, 2023).
1855:
is a paracrine that is released by immune cells in the bronchial tree. Histamine causes the smooth muscle cells of the bronchi to constrict, narrowing the airways.
4187:
890:
degradation. Thus inhibited GSK3, allows β-catenin to dissociate from APC, accumulate, and travel to nucleus. In the nucleus β-catenin associates with Lef/Tcf
949:. Once again Wnt proteins binds to and activates Frizzled so that Frizzled activates a Dishevelled protein that is tethered to the plasma membrane through a
837:, and the noncanonical Wnt/Ca pathway. Wnt proteins appear to control a wide range of developmental processes and have been seen as necessary for control of
1473:
765:
The
Hedgehog Signaling pathway is critical in proper tissue patterning and orientation during normal development of most animals. Hedgehog proteins induce
2260:
Stephen J.; Suggs, Sidney V. (1990). "Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor".
165:
10 are two of the critical players in limb development. In the forelimb initiation and limb growth in mice, axial (lengthwise) cues from the intermediate
1936:
Gospodarowicz, D.; Ferrara, N.; Schweigerer, L.; Neufeld, G. (1987). "Structural
Characterization and Biological Functions of Fibroblast Growth Factor".
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and Slimb, so that the Ci protein is not cleaved. This intact Ci protein can enter the nucleus, associate with CPB protein and act as a transcriptional
449:
ideal environments for tumors to arise. Effectively, multiple bindings of ligands to the RTK receptors overstimulates the Ras-Raf-MAPK pathway, which
92:
Although paracrine signaling elicits a diverse array of responses in the induced cells, most paracrine factors utilize a relatively streamlined set of
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1234:
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473:. Instead of carrying covalently associated tyrosine kinase domains, Jak-STAT receptors form noncovalent complexes with tyrosine kinases of the Jak (
1823:
are paracrine signaling agents. The local action of growth factor signaling plays an especially important role in the development of tissues. Also,
1409:
regulate mature ligand stability and processing, including degrading ligands in lysosomes. BMPs act by diffusing from the cells that create them.
4126:
3690:
3661:
4159:
2639:
4434:
674:) has various roles in vertebrae development, mediating signaling and regulating the organization of central nervous system, limb, and
4402:
2405:
1194:
family, which function as transcription factors. Specifically, the type I receptor, activated by the type II receptor, phosphorylates
777:
in particular. This uncontrolled activation of the
Hedgehog proteins can be caused by mutations to the signal pathway, which would be
392:
769:
in certain cells and differentiations in others. Aberrant activation of the
Hedgehog pathway has been implicated in several types of
4180:
1523:
985:
levels. Again Wnt binds and activates to
Frizzled. In this case however activated Frizzled causes a coupled G-protein to activate a
4107:
3886:
Schmierer, Bernhard; Hill, Caroline S. (2007). "TGFβ–SMAD signal transduction: Molecular specificity and functional flexibility".
3013:"Paracrine Sonic Hedgehog Signaling Contributes Significantly to Acquired Steroidogenesis in the Prostate Tumor Microenvironment"
43:
1765:
1226:
620:
Research on paracrine signaling through the JAK-STAT pathway revealed its potential in activating invasive behavior of ovarian
505:
to alter gene expression. In particular, the STATs transcribe genes that aid in cell proliferation and survival – such as myc.
150:
One of the most important functions of the FGF receptors (FGFR) is in limb development. This signaling involves nine different
114:
1338:. TGF-β proteins regulate epithelia by controlling where and when they branch to form kidney, lung, and salivary gland ducts.
388:, the binding of the receptor to the ligand also causes the trans phosphorylation of the cytoplasmic domain of the receptor.
1831:, functions in a paracrine fashion to regulate gene expression during embryonic development in higher animals. In insects,
793:
populations, and required for normal growth and regeneration of damaged organs. This may provide another possible route for
428:
encodes a tyrosine kinase receptor whose ligand is a paracrine protein called stem cell factor (SCF), which is important in
1241:
through phosphorylation. However, when a BMP ligand binds to the receptors, the phosphorylated receptor complex activates
371:. This dimerizes the transmembrane receptor to another RTK receptor, which causes the autophosphorylation and subsequent
50:
produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as
4567:
4429:
4173:
2760:"Paracrine Signaling through the JAK/STAT Pathway Activates Invasive Behavior of Ovarian Epithelial Cells in Drosophila"
805:
786:
749:. In the presence of Hedgehog, Patched no longer inhibits Smoothened. Then active Smoothened protein is able to inhibit
3011:
Lubik AA, Nouri M, Truong S, Ghaffari M, Adomat HH, Corey E, Cox ME, Li N, Guns ES, Yenki P, Pham S, Buttyan R (2016).
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4248:
4231:
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2349:"The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells"
1378:
1055:
1035:
883:
741:. In the absence of Hedgehog, the Patched receptor inhibits Smoothened action. Inhibition of Smoothened causes the
641:
470:
106:
4444:
4439:
4253:
1489:
709:
Production of the CiR transcriptional repressor when Hh is not bound to
Patched. In the diagram, "P" represents
678:
466:
364:
337:
3541:
Bandyopadhyay, Amitabha; Tsuji, Kunikazu; Cox, Karen; Harfe, Brian D.; Rosen, Vicki; Tabin, Clifford J. (2006).
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102:
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protein. In its active state the
Dishevelled protein inhibits the activity of the glycogen synthase kinase 3 (
4364:
4336:
4263:
4243:
592:
424:. In fact, mutant forms of a single RTK may play a causal role in very different types of cancer. The Kit
93:
3837:
Itoh, Fumiko; Asao, Hironobu; Sugamura, Kazuo; Heldin, Carl-Henrik; Ten Dijke, Peter; Itoh, Susumu (2001).
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217:
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1254:
1002:
502:
372:
151:
110:
3707:
2154:
Fantl, Wendy J; Johnson, Daniel E; Williams, Lewis T (1993). "Signaling by Receptor Tyrosine Kinases".
858:
721:
When Hh is bound to Patched (PTCH), Ci protein is able to act as a transcription factor in the nucleus.
670:
have been found in vertebrates: sonic hedgehog, desert hedgehog, and Indian hedgehog. Sonic hedgehog (
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70:
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3062:"A Genetic Screen in Drosophila for Identifying Novel Components of the Hedgehog Signaling Pathway"
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826:
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220:. These cells are in contact with the outer ectoderm cells, which will eventually become the lens.
118:
74:
3649:
902:
The noncanonical Wnt pathways provide a signal transduction pathway for Wnt that does not involve
3911:
3625:
3518:
3474:
3183:
3042:
2917:
2687:
2525:
2442:"Meaningful relationships: The regulation of the Ras/Raf/MEK/ERK pathway by protein interactions"
2422:
2414:
2328:
2285:
1992:
918:
843:
766:
444:
has elucidated the theory that paracrine signaling may aid in creating tumor microenvironments.
131:
66:
3839:"Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads"
3404:
Logan, Catriona Y.; Nusse, Roel (2004). "The Wnt Signaling Pathway in Development and Disease".
579:
defective IL-12-driven Th1 differentiation, increased susceptibility to intracellular pathogens
4144:
3150:
Taipale, Jussi; Beachy, Philip A. (2001). "The Hedgehog and Wnt signaling pathways in cancer".
929:
84:
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Xu, J.; Xu, J; Colvin, JS; McEwen, DG; MacArthur, CA; Coulier, F; Gao, G; Goldfarb, M (1996).
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2010:
1953:
1882:– either a paracrine hormone, or a hormone acting in both a paracrine and an endocrine fashion
950:
838:
134:. Additionally, the responding cell must also have the ability to be mechanistically induced.
4011:
Munir, Sadia; Xu, Guoxiong; Wu, Yaojiong; Yang, Burton; Lala, Peeyush K.; Peng, Chun (2004).
3592:
Attisano, Liliana; Wrana, Jeffrey L. (2002). "Signal Transduction by the TGF-β Superfamily".
3543:"Genetic Analysis of the Roles of BMP2, BMP4, and BMP7 in Limb Patterning and Skeletogenesis"
3449:
Lustig, B; Behrens, J (2003). "The Wnt signaling pathway and its role in tumor development".
3427:
2492:
Aaronson, David S.; Horvath, Curt M. (2002). "A Road Map for Those Who Don't Know JAK-STAT".
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Katz, Michael E; McCormick, Frank (1997). "Signal transduction from multiple Ras effectors".
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2123:
2082:
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2000:
1984:
1945:
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1335:
1038:" (Transforming Growth Factor) is a family of proteins that includes 33 members that encode
750:
554:
408:
368:
58:
31:
3788:
Pavletich, Nikola P.; Hata, Yigong; Lo, Akiko; Massagué, Roger S.; Pavletich, Joan (1997).
204:
Additionally, paracrine signaling of Fgf is essential in the developing eye of chicks. The
4386:
4111:
4102:
1874:
1820:
1758:
1724:
1499:
1213:
Specific TGF-β ligands will result in the activation of either the SMAD2/3 or the SMAD1/5
690:
359:
and activates the RTK pathway. This pathway begins at the cell membrane surface, where a
97:
2850:
Genes Are Coexpressed at Many Diverse Sites of Cell–Cell Interaction in the Mouse Embryo"
3805:
3605:
3163:
2505:
2202:
2167:
2031:
Lappi, Douglas A. (1995). "Tumor targeting through fibroblast growth factor receptors".
1046:
ligands bind to either Type I or Type II receptors, to create heterotetramic complexes.
420:
Paracrine signaling of growth factors between nearby cells has been shown to exacerbate
4519:
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4165:
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4053:
3569:
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3381:
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2755:
2731:
2706:
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2441:
2373:
2348:
2005:
1972:
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1401:
is crucial for kidney development, sperm synthesis, and neural tube polarization. Both
1355:
1350:, as their name suggests. However, BMPs are very multifunctional and can also regulate
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946:
782:
682:
671:
596:
486:
482:
478:
450:
441:
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47:
39:
4013:"Nodal and ALK7 Inhibit Proliferation and Induce Apoptosis in Human Trophoblast Cells"
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2989:
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2776:
2759:
2602:
2585:
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Rönnstrand, L. (2004). "Signal transduction via the stem cell factor receptor/c-Kit".
2237:
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regulates many cellular processes in developing embryo and adult organisms, including
1005:
to release intracellular calcium stores, to induce calcium-dependent gene expression.
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1879:
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Figure of the three main pathways of Wnt signaling in biological signal transduction.
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Wrana, Jeffrey L.; Ozdamar, Barish; Le Roy, Christine; Benchabane, Hassina (2008).
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Nybakken, K; Perrimon, N (2002). "Hedgehog signal transduction: Recent findings".
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3685:. Proteins and Cell Regulation. Vol. 5. Dordrecht: Springer. pp. 1–13.
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over a relatively short distance (local action), as opposed to cell signaling by
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4354:
3077:
2457:
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Yarden, Yosef; Ullrich, Axel (1988). "Growth Factor Receptor Tyrosine Kinases".
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911:
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3790:"A structural basis for mutational inactivation of the tumour suppressor Smad4"
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646:
629:
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494:
3683:
Smad Signal Transduction: Smads in Proliferation, Differentiation and Disease
2087:
2070:
1366:. They also specify the anterior/posterior axis, induce growth, and regulate
882:) enzyme. Normally active GSK3 prevents the dissociation of β-catenin to the
697:) is expressed in the gut and cartilage, important in postnatal bone growth.
4524:
4258:
3970:
Ohkawara, Bisei; Iemura, Shun-Ichiro; Ten Dijke, Peter; Ueno, Naoto (2002).
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10.1002/(SICI)1096-8628(19960503)63:1<148::AID-AJMG26>3.0.CO;2-N
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and either up-regulate or down-regulate in the expression of a target gene.
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1973:"Recent developments in the cell biology of basic fibroblast growth factor"
1775:
1648:
1299:, and TGF-β5. They are involved in positively and negatively regulation of
874:
family of proteins. The binding of Wnt to a Frizzled protein activates the
650:. Hedgehog proteins produce key signals for the establishment of limb and
3823:
3282:
3228:
2962:
2875:
2683:
2647:
2411:. If this is an intentional citation to a retracted paper, please replace
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2245:
2210:
2175:
2096:
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2014:
1957:
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Phenotype and survival of mice after knockout of some JAK or STAT genes:
407:
Diagram showing key components of a signal transduction pathway. See the
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17:
3972:"Action Range of BMP is Defined by Its N-Terminal Basic Amino Acid Core"
1988:
1949:
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promotes bone formation, causes cell death, or signals the formation of
705:
4298:
2817:
2800:
1996:
1890:
1803:
1713:
1439:
1249:. Then, the Smad2/3 or the Smad1/5 complexes form a dimer complex with
1218:
982:
770:
730:
454:
77:. Cells that produce paracrine factors secrete them into the immediate
62:
54:
3947:
3930:
3264:
3029:
3012:
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2544:
2128:
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and transmembrane Stbm protein. The active Dishevelled activates RhoA
3171:
2722:
2543:
Rawlings, Jason S.; Rosler, Kristin M.; Harrison, Douglas A. (2004).
2393:
2364:
1839:
In mature organisms, paracrine signaling is involved in responses to
1738:
1734:
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1682:
1644:
1639:
1610:
1605:
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1568:
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1334:. Ultimately, it increases the production of extracellular matrix by
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1135:
1114:
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954:
778:
675:
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213:
117:. Binding of a paracrine factor to its respective receptor initiates
3899:
3350:
3348:
3346:
2801:"Hedgehog signaling in animal development: Paradigms and principles"
311:
Development of multiple organs (including limbs, thymus, pituitary)
2586:"Cytokine signaling in 2002: new surprises in the Jak/Stat pathway"
363:
binds to its specific receptor. Ligands that bind to RTKs include
4054:"Retinoic acid synthesis and signaling during early organogenesis"
3814:
3789:
1799:
1795:
1790:
1785:
1781:
1753:
1748:
1744:
1704:
1699:
1695:
1692:
1677:
1663:
1658:
1654:
1634:
1625:
1620:
1616:
1588:
1583:
1579:
1374:
1222:
1085:
972:
928:
907:
857:
804:
716:
704:
604:
402:
83:
367:, epidermal growth factors, platelet-derived growth factors, and
4121:. Houston: OpenStax CNX. 17.1 Overview of the endocrine system.
3643:
3641:
3639:
1844:
1835:
controls growth through paracrine action on the corpora allata.
1600:
1406:
1402:
1398:
1390:
1386:
1382:
879:
344:
pathway. This signaling pathway has been highly studied, using
209:
4169:
1893:– A curated resource of signal transduction pathways in humans
2887:
2885:
2584:
O'Shea, John J; Gadina, Massimo; Schreiber, Robert D (2002).
2071:"Receptor Specificity of the Fibroblast Growth Factor Family"
603:
gene, causing a premature and constitutive activation of the
2937:"New players and puzzles in the Hedgehog signaling pathway"
725:
Members of the Hedgehog protein family act by binding to a
3301:
Chen, Xi; Yang, Jun; Evans, Paul M; Liu, Chunming (2008).
1346:
Members of the BMP family were originally found to induce
870:, Wnt proteins binds to its transmembrane receptor of the
2892:
Jacob, L.; Lum, L. (2007). "Hedgehog Signaling Pathway".
212:
becomes localized in what differentiates into the neural
3536:
3534:
3532:
981:
The noncanonical Wnt/Ca pathway regulates intracellular
226:
and survival of mice after knockout of some FGFR genes:
757:, inducing the expression of Hedgehog-response genes.
3203:"Wnt signaling: A common theme in animal development"
3109:
Evangelista, M.; Tian, H.; De Sauvage, F. J. (2006).
2112:"Finger or toe: The molecular basis of limb identity"
829:
cascades via three different pathways, the canonical
1274:
receptors directly phosphorylate non-Smad proteins.
1261:
involved in the pathway, there is only one co-SMAD,
4487:
4457:
4420:
4395:
4363:
4335:
4289:
4282:
4207:
3681:. In ten Dijke, Peter; Heldin, Carl-Henrik (eds.).
3242:
3240:
3238:
925:
The noncanonical planar cell polarity (PCP) pathway
340:and its respective receptors utilizes the receptor
65:which travel considerably longer distances via the
3929:Moustakas, Aristidis; Heldin, Carl-Henrik (2005).
3249:"Signal transduction by the Wnt family of ligands"
599:dwarfism (viable). This is due to a mutation in a
2707:"The basics of epithelial-mesenchymal transition"
3451:Journal of Cancer Research and Clinical Oncology
906:. In the noncanonical pathways, Wnt affects the
497:(important for mediating immune cell function).
3406:Annual Review of Cell and Developmental Biology
3296:
3294:
3292:
1190:The TGF-β superfamily activates members of the
737:" protein, by which the Hedgehog signal can be
3677:ten Dijke, Peter; Heldin, Carl-Henrik (2006).
933:Noncanonical Wnt Planar Cell Polarity pathway.
4181:
3749:"Crystal Structure of a Phosphorylated Smad2"
2978:Current Opinion in Genetics & Development
2941:Current Opinion in Genetics & Development
2840:Bitgood, Mark J.; McMahon, Andrew P. (1995).
2226:Current Opinion in Genetics & Development
1971:Rifkin, Daniel B.; Moscatelli, David (1989).
125:Paracrine factors induce competent responders
8:
2935:Johnson, Ronald L; Scott, Matthew P (1998).
2705:Kalluri, Raghu; Weinberg, Robert A. (2009).
957:through Dishevelled associated activator of
937:The noncanonical PCP pathway regulates cell
586:Aberrant JAK-STAT pathway and bone mutations
3652:. In Derynck, Rik; Miyazono, Kohei (eds.).
2487:
2485:
1397:, depending on the tissue it is acting on.
1375:bone morphogenetic protein receptor type II
1342:2. Bone morphogenetic protein (BMPs) family
266:Inner ear, skeletal (tail) differentiation
193:8, which also stimulates the production of
4369:
4286:
4188:
4174:
4166:
3111:"The Hedgehog Signaling Pathway in Cancer"
2425:|...|intentional=yes}}
1206:and enters the nucleus, where they act as
1202:. The R-SMAD/Co-SMAD forms a complex with
989:(PLC), which interacts with and splits PIP
297:defect, CNS development, limb development
173:5, which subsequently signals to the same
4147:at the U.S. National Library of Medicine
4077:
4028:
3987:
3946:
3862:
3813:
3764:
3723:
3650:"Signaling Receptors of the TGF-β Family"
3568:
3558:
3417:
3380:
3326:
3272:
3218:
3126:
3085:
3028:
2952:
2865:
2816:
2775:
2730:
2601:
2560:
2465:
2372:
2127:
2086:
2004:
1524:Growth and differentiation factors (GDFs)
1090:SMAD Signaling Pathway Activated by TGF-β
121:cascades, eliciting different responses.
88:Overview of signal transduction pathways.
3428:10.1146/annurev.cellbio.20.010403.113126
2149:
2147:
2064:
2062:
1533:
1530:Summary table of TGF-β signaling pathway
1474:Glial-Derived Neurotrophic Factor (GDNF)
1123:
510:
228:
2026:
2024:
1907:
1494:Involved in mammalian sex determination
898:The noncanonical Wnt signaling pathways
781:independent, or a mutation that causes
666:. At least three "Drosophila" hedgehog
477:) class. These receptors bind are for
332:Receptor tyrosine kinase (RTK) pathway
3888:Nature Reviews Molecular Cell Biology
3355:Komiya, Yuko; Habas, Raymond (2008).
3303:"Wnt signaling: The good and the bad"
1377:(BMPR2). Some of the proteins of the
761:Hedgehog signaling pathway and cancer
138:Fibroblast growth factor (FGF) family
7:
3307:Acta Biochimica et Biophysica Sinica
2628:American Journal of Medical Genetics
2305:Cellular and Molecular Life Sciences
1330:and inhibits the degradation of the
4435:Transcription preinitiation complex
3706:Moustakas, Aristidis (2002-09-01).
2799:Ingham, P. W.; McMahon, AP (2001).
2203:10.1146/annurev.bi.57.070188.002303
2168:10.1146/annurev.bi.62.070193.002321
1322:TGF-β1 stimulates the synthesis of
1001:can then bind to a receptor on the
854:The canonical Wnt signaling pathway
733:" receptor, which is bound to the "
658:of adult tissues, involved in late
4403:Signal transducing adaptor protein
3357:"Wnt signal transduction pathways"
3201:Cadigan, K. M.; Nusse, R. (1997).
3060:Collins, R. T.; Cohen, SM (2005).
1843:, tissue repair, the formation of
1413:Other members of TGF-β superfamily
1099:There are three classes of SMADs:
862:Canonical Wnt pathway without Wnt.
835:planar cell polarity (PCP) pathway
817:family includes a large number of
25:
4052:Duester, Gregg (September 2008).
2711:Journal of Clinical Investigation
2353:Journal of Clinical Investigation
1121:Examples of SMADs in each class:
1009:Wnt signaling pathways and cancer
977:Noncanonical Wnt/calcium pathway.
96:and pathways. In fact, different
4106: This article incorporates
4101:
3319:10.1111/j.1745-7270.2008.00440.x
2545:"The JAK/STAT signaling pathway"
628:transition is highly evident in
457:and invasive capacity of cells.
27:Form of localized cell signaling
4017:Journal of Biological Chemistry
3656:. CSHL Press. pp. 151–77.
3017:International Journal of Cancer
2075:Journal of Biological Chemistry
1198:that then bind to the co-SMAD,
969:The noncanonical Wnt/Ca pathway
1233:receptor complex can activate
1110:Common-mediator SMAD (Co-SMAD)
280:Inner cell mass proliferation
1:
3989:10.1016/S0960-9822(01)00684-4
3766:10.1016/S1097-2765(01)00421-X
3128:10.1158/1078-0432.CCR-06-1736
2990:10.1016/S0959-437X(02)00333-7
2954:10.1016/S0959-437X(98)80117-2
2777:10.1016/S0092-8674(01)00607-9
2603:10.1016/S0092-8674(02)00701-8
2238:10.1016/S0959-437X(97)80112-8
2191:Annual Review of Biochemistry
2156:Annual Review of Biochemistry
201:10 results in limbless mice.
4160:Dorland's Medical Dictionary
3560:10.1371/journal.pgen.0020216
2676:10.1016/0092-8674(94)90302-6
2274:10.1016/0092-8674(90)90302-U
1510:Forms receptor complex with
1278:Members of TGF-β superfamily
1229:binds to the receptors, the
825:. The Wnt proteins activate
787:androgen deprivation therapy
465:In addition to RTK pathway,
336:Paracrine signaling through
3078:10.1534/genetics.104.039420
1977:The Journal of Cell Biology
1673:Bone morphogenetic proteins
1537:TGF Beta superfamily ligand
1490:Müllerian Inhibitory Factor
1453:Nerve cell survival factors
616:JAK-STAT pathway and cancer
568:Tissue specific phenotypes
4584:
4070:10.1016/j.cell.2008.09.002
2033:Seminars in Cancer Biology
1516:Activin A Type 1C receptor
1512:Activin A Type 1B receptor
1506:Activin A Type 2B receptor
886:protein, which results in
797:via the Hedgehog pathway.
701:Hedgehog signaling pathway
654:of fruit flies as well as
542:Failure in erythropoiesis
471:JAK-STAT signaling pathway
143:hundreds of different FGF
4372:
3507:10.1007/s12015-007-0001-y
3463:10.1007/s00432-003-0431-0
2458:10.1042/0264-6021:3510289
2317:10.1007/s00018-004-4189-6
1103:Receptor-regulated SMAD (
467:fibroblast growth factors
365:fibroblast growth factors
338:fibroblast growth factors
4515:Neuroendocrine signaling
4149:Medical Subject Headings
4119:Anatomy & Physiology
3931:"Non-Smad TGF-β signals"
3855:10.1093/emboj/20.15.4132
3708:"Smad signaling network"
3247:Dale, Trevor C. (1998).
3115:Clinical Cancer Research
2088:10.1074/jbc.271.25.15292
1257:. Though there are many
846:, cell morphology, cell
348:eyes and human cancers.
103:fibroblast growth factor
3935:Journal of Cell Science
3725:10.1242/jcs.115.17.3355
3712:Journal of Cell Science
3614:10.1126/science.1071809
3253:The Biochemical Journal
3207:Genes & Development
2906:10.1126/stke.4072007cm6
2805:Genes & Development
2549:Journal of Cell Science
2514:10.1126/science.1071545
2446:The Biochemical Journal
1303:, the formation of the
642:Hedgehog protein family
593:thanatophoric dysplasia
416:RTK receptor and cancer
351:Binding of FGF to FGFR
325:Cerebellar Development
189:to begin production of
185:10 then signals to the
71:juxtacrine interactions
4377:cAMP-dependent pathway
4030:10.1074/jbc.M400641200
3220:10.1101/gad.11.24.3286
2867:10.1006/dbio.1995.0010
2440:Kolch, Walter (2000).
2045:10.1006/scbi.1995.0036
1886:MAPK signaling pathway
1865:cAMP dependent pathway
1478:Needed for kidney and
1317:TGF-β type II receptor
1091:
978:
934:
863:
810:
722:
714:
685:) is expressed in the
607:transcription factor.
469:can also activate the
436:RTK pathway and cancer
412:
89:
44:cellular communication
4503:Synaptic transmission
4499:Neurocrine signaling
4422:Transcription factors
4269:PI3K/AKT/mTOR pathway
2854:Developmental Biology
2417:|...}}
2388:(Retracted, see
1827:, the active form of
1373:The BMPs bind to the
1287:This family includes
1255:transcription factors
1217:. For instance, when
1208:transcription factors
1089:
1003:endoplasmic reticulum
976:
932:
861:
808:
720:
708:
624:. This epithelial to
503:transcription factors
406:
373:conformational change
152:alternatively spliced
87:
4110:available under the
3373:10.4161/org.4.2.5851
1332:extracellular matrix
1305:extracellular matrix
1016:degenerative disease
892:transcription factor
775:Basal Cell Carcinoma
531:Neurologic Deficits
411:article for details.
4568:Signal transduction
4532:Mechanotransduction
4520:Exocrine signalling
4327:Signaling molecules
4201:Signal transduction
4145:Paracrine+Signaling
3806:1997Natur.388R..87S
3606:2002Sci...296.1646A
3164:2001Natur.411..349T
2506:2002Sci...296.1653A
1989:10.1083/jcb.109.1.1
1950:10.1210/edrv-8-2-95
1916:"Paracrine Factors"
1897:Paracrine regulator
1870:Crosstalk (biology)
833:, the noncanonical
827:signal transduction
743:Cubitus interruptus
693:. Indian hedgehog (
681:. Desert hedgehog (
553:Human dwarfism and
119:signal transduction
75:autocrine signaling
36:paracrine signaling
4542:Ion channel gating
4274:Integrin receptors
4208:Signaling pathways
2818:10.1101/gad.938601
2756:Montell, Denise J.
2754:Silver, Debra L.;
2311:(19–20): 2535–48.
2110:Logan, M. (2003).
1558:Ligand Inhibitors
1092:
979:
935:
919:gene transcription
864:
844:cell proliferation
811:
767:cell proliferation
723:
715:
413:
232:FGFR Knockout Gene
90:
67:circulatory system
4555:
4554:
4537:Phototransduction
4495:Intracrine action
4453:
4452:
4416:
4415:
4304:Neurotransmitters
4128:978-1-947172-04-3
3948:10.1242/jcs.02554
3692:978-1-4020-4709-1
3679:"The Smad family"
3663:978-0-87969-752-5
3495:Stem Cell Reviews
3265:10.1042/bj3290209
3030:10.1002/ijc.30450
2562:10.1242/jcs.00963
2129:10.1242/dev.00956
1938:Endocrine Reviews
1809:
1808:
1188:
1187:
1113:Inhibitory SMAD (
1030:TGF-β superfamily
868:canonical pathway
850:, and cell fate.
583:
582:
329:
328:
197:10. Deletion of
157:of the receptor.
115:TGF-β superfamily
59:endocrine factors
52:paracrine factors
16:(Redirected from
4575:
4508:Chemical synapse
4408:Scaffold protein
4370:
4365:Second messenger
4291:Receptor ligands
4287:
4190:
4183:
4176:
4167:
4133:
4132:
4105:
4098:
4092:
4091:
4081:
4049:
4043:
4042:
4032:
4023:(30): 31277–86.
4008:
4002:
4001:
3991:
3967:
3961:
3960:
3950:
3926:
3920:
3919:
3883:
3877:
3876:
3866:
3843:The EMBO Journal
3834:
3828:
3827:
3817:
3785:
3779:
3778:
3768:
3744:
3738:
3737:
3727:
3703:
3697:
3696:
3674:
3668:
3667:
3654:The TGF-β Family
3645:
3634:
3633:
3600:(5573): 1646–7.
3589:
3583:
3582:
3572:
3562:
3538:
3527:
3526:
3489:
3483:
3482:
3446:
3440:
3439:
3421:
3401:
3395:
3394:
3384:
3352:
3341:
3340:
3330:
3298:
3287:
3286:
3276:
3259:(Pt 2): 209–23.
3244:
3233:
3232:
3222:
3213:(24): 3286–305.
3198:
3192:
3191:
3172:10.1038/35077219
3158:(6835): 349–54.
3147:
3141:
3140:
3130:
3106:
3100:
3099:
3089:
3057:
3051:
3050:
3032:
3008:
3002:
3001:
2973:
2967:
2966:
2956:
2932:
2926:
2925:
2889:
2880:
2879:
2869:
2837:
2831:
2830:
2820:
2796:
2790:
2789:
2779:
2751:
2745:
2744:
2734:
2723:10.1172/JCI39104
2702:
2696:
2695:
2658:
2652:
2651:
2622:
2616:
2615:
2605:
2581:
2575:
2574:
2564:
2540:
2534:
2533:
2500:(5573): 1653–5.
2489:
2480:
2479:
2469:
2437:
2431:
2430:
2428:
2426:
2418:
2407:Retraction Watch
2394:10.1172/JCI87345
2386:
2376:
2365:10.1172/JCI22758
2343:
2337:
2336:
2300:
2294:
2293:
2256:
2250:
2249:
2221:
2215:
2214:
2186:
2180:
2179:
2151:
2142:
2141:
2131:
2107:
2101:
2100:
2090:
2066:
2057:
2056:
2028:
2019:
2018:
2008:
1968:
1962:
1961:
1933:
1927:
1926:
1924:
1922:
1912:
1821:clotting factors
1541:Type II Receptor
1534:
1336:epithelial cells
1269:Non-SMAD pathway
1124:
961:(Daam1) and the
622:epithelial cells
555:craniosynostosis
511:
493:formation), and
461:JAK-STAT pathway
409:MAPK/ERK pathway
369:stem cell factor
229:
32:cellular biology
21:
4583:
4582:
4578:
4577:
4576:
4574:
4573:
4572:
4558:
4557:
4556:
4551:
4483:
4449:
4412:
4391:
4387:Lipid signaling
4359:
4331:
4278:
4203:
4194:
4141:
4136:
4129:
4116:
4099:
4095:
4051:
4050:
4046:
4010:
4009:
4005:
3976:Current Biology
3969:
3968:
3964:
3941:(16): 3573–84.
3928:
3927:
3923:
3900:10.1038/nrm2297
3885:
3884:
3880:
3849:(15): 4132–42.
3836:
3835:
3831:
3800:(6637): 87–93.
3787:
3786:
3782:
3746:
3745:
3741:
3705:
3704:
3700:
3693:
3676:
3675:
3671:
3664:
3647:
3646:
3637:
3591:
3590:
3586:
3540:
3539:
3530:
3491:
3490:
3486:
3448:
3447:
3443:
3403:
3402:
3398:
3354:
3353:
3344:
3300:
3299:
3290:
3246:
3245:
3236:
3200:
3199:
3195:
3149:
3148:
3144:
3108:
3107:
3103:
3059:
3058:
3054:
3010:
3009:
3005:
2975:
2974:
2970:
2934:
2933:
2929:
2891:
2890:
2883:
2839:
2838:
2834:
2811:(23): 3059–87.
2798:
2797:
2793:
2753:
2752:
2748:
2704:
2703:
2699:
2660:
2659:
2655:
2624:
2623:
2619:
2583:
2582:
2578:
2542:
2541:
2537:
2491:
2490:
2483:
2439:
2438:
2434:
2420:
2412:
2410:
2387:
2345:
2344:
2340:
2302:
2301:
2297:
2258:
2257:
2253:
2223:
2222:
2218:
2188:
2187:
2183:
2153:
2152:
2145:
2122:(26): 6401–10.
2109:
2108:
2104:
2081:(25): 15292–7.
2068:
2067:
2060:
2030:
2029:
2022:
1970:
1969:
1965:
1935:
1934:
1930:
1920:
1918:
1914:
1913:
1909:
1905:
1875:Lipid signaling
1861:
1838:
1814:
1546:Type I Receptor
1532:
1483:differentiation
1446:, gonadal, and
1415:
1364:differentiation
1344:
1315:. They bind to
1307:between cells,
1285:
1283:1. TGF-β family
1280:
1271:
1097:
1064:differentiation
1052:
1032:
1011:
1000:
996:
993:into DAG and IP
992:
971:
959:morphogenesis 1
951:Prickle protein
927:
900:
856:
803:
763:
703:
691:spermatogenesis
638:
636:Hedgehog family
618:
588:
489:(important for
481:(important for
463:
438:
418:
393:adaptor protein
384:, and into the
334:
140:
127:
28:
23:
22:
15:
12:
11:
5:
4581:
4579:
4571:
4570:
4560:
4559:
4553:
4552:
4550:
4549:
4544:
4539:
4534:
4529:
4528:
4527:
4517:
4512:
4511:
4510:
4505:
4497:
4491:
4489:
4488:Other concepts
4485:
4484:
4482:
4481:
4476:
4467:
4461:
4459:
4455:
4454:
4451:
4450:
4448:
4447:
4442:
4437:
4432:
4426:
4424:
4418:
4417:
4414:
4413:
4411:
4410:
4405:
4399:
4397:
4393:
4392:
4390:
4389:
4384:
4379:
4373:
4367:
4361:
4360:
4358:
4357:
4352:
4347:
4341:
4339:
4333:
4332:
4330:
4329:
4324:
4322:Growth factors
4319:
4314:
4301:
4295:
4293:
4284:
4280:
4279:
4277:
4276:
4271:
4266:
4261:
4256:
4251:
4246:
4241:
4240:
4239:
4234:
4224:
4219:
4217:
4211:
4209:
4205:
4204:
4197:Cell signaling
4195:
4193:
4192:
4185:
4178:
4170:
4164:
4163:
4152:
4140:
4139:External links
4137:
4135:
4134:
4127:
4093:
4044:
4003:
3962:
3921:
3894:(12): 970–82.
3878:
3829:
3780:
3759:(6): 1277–89.
3753:Molecular Cell
3739:
3718:(17): 3355–6.
3698:
3691:
3669:
3662:
3635:
3584:
3528:
3484:
3457:(4): 199–221.
3441:
3419:10.1.1.322.311
3396:
3342:
3288:
3234:
3193:
3142:
3121:(20): 5924–8.
3101:
3052:
3023:(2): 358–369.
3003:
2968:
2927:
2894:Science's STKE
2881:
2832:
2791:
2746:
2697:
2653:
2617:
2596:(2): S121–31.
2576:
2535:
2481:
2452:(2): 289–305.
2432:
2359:(4): 1068–81.
2338:
2295:
2251:
2216:
2181:
2143:
2102:
2058:
2020:
1963:
1928:
1906:
1904:
1901:
1900:
1899:
1894:
1888:
1883:
1877:
1872:
1867:
1860:
1857:
1813:
1810:
1807:
1806:
1793:
1788:
1779:
1773:
1768:
1762:
1761:
1756:
1751:
1742:
1732:
1727:
1721:
1720:
1707:
1702:
1690:
1680:
1675:
1669:
1668:
1666:
1661:
1652:
1642:
1637:
1631:
1630:
1628:
1623:
1614:
1608:
1603:
1597:
1596:
1591:
1586:
1577:
1571:
1566:
1560:
1559:
1556:
1553:
1548:
1543:
1538:
1531:
1528:
1527:
1526:
1521:
1520:
1519:
1508:
1497:
1496:
1495:
1487:
1486:
1485:
1480:enteric neuron
1471:
1470:
1469:
1454:
1451:
1436:
1424:Activin Family
1421:
1414:
1411:
1356:cell migration
1348:bone formation
1343:
1340:
1284:
1281:
1279:
1276:
1270:
1267:
1231:phosphorylated
1186:
1185:
1176:
1170:
1169:
1164:
1160:
1159:
1138:
1132:
1131:
1128:
1119:
1118:
1111:
1108:
1096:
1093:
1051:
1048:
1031:
1028:
1010:
1007:
998:
994:
990:
970:
967:
926:
923:
899:
896:
855:
852:
802:
799:
783:overexpression
762:
759:
702:
699:
637:
634:
617:
614:
597:achondroplasic
587:
584:
581:
580:
577:
574:
570:
569:
566:
563:
559:
558:
551:
548:
544:
543:
540:
537:
533:
532:
529:
526:
522:
521:
518:
515:
487:thrombopoietin
483:erythropoiesis
479:erythropoietin
462:
459:
442:thyroid cancer
437:
434:
426:proto-oncogene
422:carcinogenesis
417:
414:
353:phosphorylates
333:
330:
327:
326:
323:
320:
313:
312:
309:
306:
299:
298:
292:
289:
282:
281:
278:
275:
268:
267:
264:
261:
254:
253:
250:
247:
240:
239:
236:
233:
139:
136:
126:
123:
105:(FGF) family,
40:cell signaling
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
4580:
4569:
4566:
4565:
4563:
4548:
4545:
4543:
4540:
4538:
4535:
4533:
4530:
4526:
4523:
4522:
4521:
4518:
4516:
4513:
4509:
4506:
4504:
4501:
4500:
4498:
4496:
4493:
4492:
4490:
4486:
4480:
4477:
4475:
4471:
4468:
4466:
4463:
4462:
4460:
4456:
4446:
4443:
4441:
4438:
4436:
4433:
4431:
4428:
4427:
4425:
4423:
4419:
4409:
4406:
4404:
4401:
4400:
4398:
4394:
4388:
4385:
4383:
4380:
4378:
4375:
4374:
4371:
4368:
4366:
4362:
4356:
4353:
4351:
4350:Intracellular
4348:
4346:
4343:
4342:
4340:
4338:
4334:
4328:
4325:
4323:
4320:
4318:
4315:
4313:
4312:Neurohormones
4309:
4308:Neuropeptides
4305:
4302:
4300:
4297:
4296:
4294:
4292:
4288:
4285:
4281:
4275:
4272:
4270:
4267:
4265:
4262:
4260:
4259:Fas apoptosis
4257:
4255:
4252:
4250:
4247:
4245:
4242:
4238:
4235:
4233:
4230:
4229:
4228:
4225:
4223:
4220:
4218:
4216:
4213:
4212:
4210:
4206:
4202:
4198:
4191:
4186:
4184:
4179:
4177:
4172:
4171:
4168:
4162:
4161:
4156:
4153:
4150:
4146:
4143:
4142:
4138:
4130:
4124:
4120:
4115:
4113:
4109:
4104:
4097:
4094:
4089:
4085:
4080:
4075:
4071:
4067:
4064:(6): 921–31.
4063:
4059:
4055:
4048:
4045:
4040:
4036:
4031:
4026:
4022:
4018:
4014:
4007:
4004:
3999:
3995:
3990:
3985:
3981:
3977:
3973:
3966:
3963:
3958:
3954:
3949:
3944:
3940:
3936:
3932:
3925:
3922:
3917:
3913:
3909:
3905:
3901:
3897:
3893:
3889:
3882:
3879:
3874:
3870:
3865:
3860:
3856:
3852:
3848:
3844:
3840:
3833:
3830:
3825:
3821:
3816:
3815:10.1038/40431
3811:
3807:
3803:
3799:
3795:
3791:
3784:
3781:
3776:
3772:
3767:
3762:
3758:
3754:
3750:
3743:
3740:
3735:
3731:
3726:
3721:
3717:
3713:
3709:
3702:
3699:
3694:
3688:
3684:
3680:
3673:
3670:
3665:
3659:
3655:
3651:
3644:
3642:
3640:
3636:
3631:
3627:
3623:
3619:
3615:
3611:
3607:
3603:
3599:
3595:
3588:
3585:
3580:
3576:
3571:
3566:
3561:
3556:
3552:
3548:
3547:PLOS Genetics
3544:
3537:
3535:
3533:
3529:
3524:
3520:
3516:
3512:
3508:
3504:
3500:
3496:
3488:
3485:
3480:
3476:
3472:
3468:
3464:
3460:
3456:
3452:
3445:
3442:
3437:
3433:
3429:
3425:
3420:
3415:
3411:
3407:
3400:
3397:
3392:
3388:
3383:
3378:
3374:
3370:
3366:
3362:
3361:Organogenesis
3358:
3351:
3349:
3347:
3343:
3338:
3334:
3329:
3324:
3320:
3316:
3313:(7): 577–94.
3312:
3308:
3304:
3297:
3295:
3293:
3289:
3284:
3280:
3275:
3270:
3266:
3262:
3258:
3254:
3250:
3243:
3241:
3239:
3235:
3230:
3226:
3221:
3216:
3212:
3208:
3204:
3197:
3194:
3189:
3185:
3181:
3177:
3173:
3169:
3165:
3161:
3157:
3153:
3146:
3143:
3138:
3134:
3129:
3124:
3120:
3116:
3112:
3105:
3102:
3097:
3093:
3088:
3083:
3079:
3075:
3072:(1): 173–84.
3071:
3067:
3063:
3056:
3053:
3048:
3044:
3040:
3036:
3031:
3026:
3022:
3018:
3014:
3007:
3004:
2999:
2995:
2991:
2987:
2984:(5): 503–11.
2983:
2979:
2972:
2969:
2964:
2960:
2955:
2950:
2946:
2942:
2938:
2931:
2928:
2923:
2919:
2915:
2911:
2907:
2903:
2899:
2895:
2888:
2886:
2882:
2877:
2873:
2868:
2863:
2860:(1): 126–38.
2859:
2855:
2851:
2849:
2845:
2836:
2833:
2828:
2824:
2819:
2814:
2810:
2806:
2802:
2795:
2792:
2787:
2783:
2778:
2773:
2770:(7): 831–41.
2769:
2765:
2761:
2757:
2750:
2747:
2742:
2738:
2733:
2728:
2724:
2720:
2717:(6): 1420–8.
2716:
2712:
2708:
2701:
2698:
2693:
2689:
2685:
2681:
2677:
2673:
2670:(2): 335–42.
2669:
2665:
2657:
2654:
2649:
2645:
2641:
2637:
2634:(1): 148–54.
2633:
2629:
2621:
2618:
2613:
2609:
2604:
2599:
2595:
2591:
2587:
2580:
2577:
2572:
2568:
2563:
2558:
2555:(8): 1281–3.
2554:
2550:
2546:
2539:
2536:
2531:
2527:
2523:
2519:
2515:
2511:
2507:
2503:
2499:
2495:
2488:
2486:
2482:
2477:
2473:
2468:
2463:
2459:
2455:
2451:
2447:
2443:
2436:
2433:
2424:
2416:
2409:
2408:
2403:
2399:
2395:
2391:
2384:
2380:
2375:
2370:
2366:
2362:
2358:
2354:
2350:
2342:
2339:
2334:
2330:
2326:
2322:
2318:
2314:
2310:
2306:
2299:
2296:
2291:
2287:
2283:
2279:
2275:
2271:
2268:(1): 213–24.
2267:
2263:
2255:
2252:
2247:
2243:
2239:
2235:
2231:
2227:
2220:
2217:
2212:
2208:
2204:
2200:
2196:
2192:
2185:
2182:
2177:
2173:
2169:
2165:
2161:
2157:
2150:
2148:
2144:
2139:
2135:
2130:
2125:
2121:
2117:
2113:
2106:
2103:
2098:
2094:
2089:
2084:
2080:
2076:
2072:
2065:
2063:
2059:
2054:
2050:
2046:
2042:
2039:(5): 279–88.
2038:
2034:
2027:
2025:
2021:
2016:
2012:
2007:
2002:
1998:
1994:
1990:
1986:
1982:
1978:
1974:
1967:
1964:
1959:
1955:
1951:
1947:
1944:(2): 95–114.
1943:
1939:
1932:
1929:
1917:
1911:
1908:
1902:
1898:
1895:
1892:
1889:
1887:
1884:
1881:
1880:Local hormone
1878:
1876:
1873:
1871:
1868:
1866:
1863:
1862:
1858:
1856:
1854:
1850:
1846:
1842:
1836:
1834:
1830:
1826:
1825:retinoic acid
1822:
1818:
1817:Growth factor
1811:
1805:
1801:
1797:
1794:
1792:
1789:
1787:
1783:
1780:
1777:
1774:
1772:
1769:
1767:
1764:
1763:
1760:
1757:
1755:
1752:
1750:
1746:
1743:
1740:
1736:
1733:
1731:
1728:
1726:
1723:
1722:
1719:
1715:
1711:
1708:
1706:
1703:
1701:
1697:
1694:
1691:
1688:
1684:
1681:
1679:
1676:
1674:
1671:
1670:
1667:
1665:
1662:
1660:
1656:
1653:
1650:
1646:
1643:
1641:
1638:
1636:
1633:
1632:
1629:
1627:
1624:
1622:
1618:
1615:
1612:
1609:
1607:
1604:
1602:
1599:
1598:
1595:
1592:
1590:
1587:
1585:
1581:
1578:
1575:
1572:
1570:
1567:
1565:
1562:
1561:
1557:
1554:
1552:
1549:
1547:
1544:
1542:
1539:
1536:
1535:
1529:
1525:
1522:
1517:
1513:
1509:
1507:
1503:
1502:
1501:
1498:
1493:
1492:
1491:
1488:
1484:
1481:
1477:
1476:
1475:
1472:
1467:
1463:
1459:
1455:
1452:
1449:
1445:
1441:
1437:
1435:
1431:
1430:embryogenesis
1427:
1426:
1425:
1422:
1420:
1417:
1416:
1412:
1410:
1408:
1404:
1400:
1396:
1392:
1388:
1384:
1380:
1376:
1371:
1369:
1365:
1361:
1360:cell division
1357:
1353:
1349:
1341:
1339:
1337:
1333:
1329:
1325:
1320:
1318:
1314:
1313:embryogenesis
1310:
1306:
1302:
1301:cell division
1298:
1294:
1290:
1282:
1277:
1275:
1268:
1266:
1264:
1260:
1256:
1252:
1248:
1244:
1240:
1236:
1232:
1228:
1224:
1220:
1216:
1211:
1209:
1205:
1201:
1197:
1193:
1184:
1180:
1177:
1175:
1172:
1171:
1168:
1165:
1162:
1161:
1158:
1154:
1150:
1146:
1142:
1139:
1137:
1134:
1133:
1129:
1126:
1125:
1122:
1116:
1112:
1109:
1106:
1102:
1101:
1100:
1094:
1088:
1084:
1081:
1077:
1073:
1069:
1065:
1061:
1057:
1056:TGF-β pathway
1050:TGF-β pathway
1049:
1047:
1045:
1041:
1037:
1029:
1027:
1023:
1021:
1017:
1008:
1006:
1004:
988:
987:phospholipase
984:
975:
968:
966:
964:
960:
956:
952:
948:
944:
940:
931:
924:
922:
920:
916:
913:
909:
905:
897:
895:
893:
889:
885:
881:
877:
873:
869:
860:
853:
851:
849:
845:
840:
836:
832:
828:
824:
823:glycoproteins
820:
816:
807:
800:
798:
796:
795:tumorigenesis
792:
788:
784:
780:
776:
772:
768:
760:
758:
756:
752:
748:
744:
740:
736:
732:
728:
727:transmembrane
719:
712:
707:
700:
698:
696:
692:
688:
687:Sertoli cells
684:
680:
677:
673:
669:
665:
664:metamorphosis
661:
660:embryogenesis
657:
653:
649:
648:
643:
635:
633:
631:
627:
623:
615:
613:
610:
606:
602:
598:
595:(lethal) and
594:
585:
578:
575:
572:
571:
567:
564:
561:
560:
556:
552:
549:
546:
545:
541:
538:
535:
534:
530:
527:
524:
523:
519:
516:
514:Knockout Gene
513:
512:
509:
506:
504:
498:
496:
492:
488:
484:
480:
476:
472:
468:
460:
458:
456:
452:
451:overexpresses
447:
443:
435:
433:
431:
430:hematopoiesis
427:
423:
415:
410:
405:
401:
398:
394:
389:
387:
383:
382:lipid bilayer
378:
377:homodimerized
374:
370:
366:
362:
358:
354:
349:
347:
343:
339:
331:
324:
321:
318:
315:
314:
310:
307:
304:
301:
300:
296:
293:
290:
287:
284:
283:
279:
276:
273:
270:
269:
265:
262:
259:
256:
255:
251:
248:
245:
242:
241:
237:
234:
231:
230:
227:
225:
221:
219:
215:
211:
207:
202:
200:
196:
192:
188:
184:
180:
176:
172:
168:
164:
160:
156:
153:
148:
146:
137:
135:
133:
124:
122:
120:
116:
112:
108:
104:
99:
95:
86:
82:
80:
79:extracellular
76:
72:
68:
64:
60:
56:
53:
49:
45:
41:
38:is a form of
37:
33:
19:
4547:Gap junction
4382:Ca signaling
4345:Cell surface
4158:
4118:
4100:
4096:
4061:
4057:
4047:
4020:
4016:
4006:
3982:(3): 205–9.
3979:
3975:
3965:
3938:
3934:
3924:
3891:
3887:
3881:
3846:
3842:
3832:
3797:
3793:
3783:
3756:
3752:
3742:
3715:
3711:
3701:
3682:
3672:
3653:
3597:
3593:
3587:
3553:(12): e216.
3550:
3546:
3501:(1): 18–29.
3498:
3494:
3487:
3454:
3450:
3444:
3409:
3405:
3399:
3367:(2): 68–75.
3364:
3360:
3310:
3306:
3256:
3252:
3210:
3206:
3196:
3155:
3151:
3145:
3118:
3114:
3104:
3069:
3065:
3055:
3020:
3016:
3006:
2981:
2977:
2971:
2947:(4): 450–6.
2944:
2940:
2930:
2900:(407): cm6.
2897:
2893:
2857:
2853:
2847:
2843:
2835:
2808:
2804:
2794:
2767:
2763:
2749:
2714:
2710:
2700:
2667:
2663:
2656:
2631:
2627:
2620:
2593:
2589:
2579:
2552:
2548:
2538:
2497:
2493:
2449:
2445:
2435:
2421:{{
2413:{{
2406:
2404:,
2356:
2352:
2341:
2308:
2304:
2298:
2265:
2261:
2254:
2229:
2225:
2219:
2194:
2190:
2184:
2159:
2155:
2119:
2115:
2105:
2078:
2074:
2036:
2032:
1980:
1976:
1966:
1941:
1937:
1931:
1919:. Retrieved
1910:
1847:, and blood
1837:
1833:Allatostatin
1815:
1456:3 Activins:
1448:hypothalamic
1434:osteogenesis
1428:Involved in
1372:
1345:
1321:
1286:
1272:
1227:TGF-β ligand
1212:
1189:
1120:
1098:
1095:SMAD pathway
1053:
1033:
1024:
1012:
980:
936:
915:cytoskeleton
912:microtubular
901:
865:
812:
764:
724:
689:involved in
645:
639:
619:
589:
507:
499:
475:Janus kinase
464:
440:Research on
439:
419:
390:
350:
345:
335:
316:
302:
295:Gastrulation
285:
271:
257:
243:
222:
205:
203:
198:
194:
190:
182:
178:
170:
162:
158:
149:
141:
128:
113:family, and
91:
51:
42:, a type of
35:
29:
4458:By distance
4396:Assistants:
4355:Co-receptor
4155:"paracrine"
3412:: 781–810.
2232:(1): 75–9.
2116:Development
1845:scar tissue
1594:Follistatin
1381:family are
1368:homeostasis
1328:fibronectin
1319:(TGFBRII).
1253:and become
1072:homeostasis
1060:cell growth
963:Rac protein
917:as well as
876:Dishevelled
831:Wnt pathway
815:Wnt protein
656:homeostasis
626:mesenchymal
609:Chondrocyte
177:to produce
46:in which a
4525:Pheromones
4465:Juxtacrine
2197:: 443–78.
2162:: 453–81.
1983:(1): 1–6.
1903:References
1466:Activin AB
1419:Vg1 Family
939:morphology
801:Wnt family
739:transduced
735:Smoothened
647:Drosophila
630:metastasis
557:syndromes
520:Phenotype
495:interferon
346:Drosophila
238:Phenotype
4479:Endocrine
4474:Paracrine
4470:Autocrine
4337:Receptors
4317:Cytokines
4112:CC BY 4.0
3414:CiteSeerX
2423:retracted
2415:retracted
1853:Histamine
1841:allergens
1829:vitamin A
1564:Activin A
1504:Binds to
1462:Activin B
1458:Activin A
1444:pituitary
1438:Regulate
1395:epidermis
1352:apoptosis
1309:apoptosis
1080:threonine
1068:apoptosis
904:β-catenin
888:β-catenin
791:stem-cell
755:activator
747:repressor
711:phosphate
652:body plan
455:mitogenic
446:Chemokine
386:cytoplasm
355:the idle
224:Phenotype
218:optic cup
169:produces
132:competent
94:receptors
18:Paracrine
4562:Category
4299:Hormones
4249:JAK-STAT
4237:MAPK/ERK
4232:TGF beta
4114:license.
4088:18805086
4039:15150278
3998:11839272
3957:16105881
3908:18000526
3873:11483516
3775:11779503
3734:12154066
3630:84138159
3622:12040180
3579:17194222
3523:25793825
3515:17873378
3479:28959851
3471:12707770
3436:15473860
3391:19279717
3337:18604449
3180:11357142
3137:17062662
3096:15744048
3066:Genetics
3039:27672740
2998:12200154
2922:35653781
2914:17925577
2844:Hedgehog
2827:11731473
2786:11779460
2758:(2001).
2741:19487818
2692:20325070
2612:11983158
2571:15020666
2530:20857536
2522:12040185
2476:11023813
2402:27035814
2383:15761501
2325:15526160
2290:39924379
2138:14660539
1859:See also
1849:clotting
1812:Examples
1737:(ALK4),
1685:(ALK3),
1647:(ALK4),
1514:or with
1450:hormones
1324:collagen
1204:importin
947:movement
943:division
872:Frizzled
848:motility
819:cysteine
679:polarity
668:homologs
517:Survival
491:platelet
342:tyrosine
252:Unclear
235:Survival
187:ectoderm
175:mesoderm
167:mesoderm
155:isoforms
145:isoforms
109:family,
107:Hedgehog
63:hormones
4430:General
4254:Akt/PKB
4079:2632951
3824:9214508
3802:Bibcode
3602:Bibcode
3594:Science
3570:1713256
3382:2634250
3328:2532600
3283:9425102
3274:1219034
3229:9407023
3188:4414768
3160:Bibcode
3087:1449730
3047:2354209
2963:9729722
2876:7589793
2732:2689101
2684:7913883
2648:8723101
2502:Bibcode
2494:Science
2467:1221363
2374:1062891
2333:2602233
2282:1698556
2246:9024640
2211:3052279
2176:7688944
2097:8663044
2053:8562905
2015:2545723
2006:2115467
1997:1613457
1958:2440668
1921:27 July
1891:Netpath
1804:Decorin
1778:(ALK5)
1771:TGFβRII
1741:(ALK7)
1714:Chordin
1689:(ALK6)
1651:(ALK5)
1613:(ALK4)
1576:(ALK4)
1555:Co-SMAD
1551:R-SMADs
1440:insulin
1259:R-SMADs
1219:activin
1215:R-SMADs
1196:R-SMADs
1163:Co-SMAD
1157:SMAD8/9
1040:dimeric
983:calcium
866:In the
839:spindle
771:cancers
731:Patched
375:of the
216:of the
55:diffuse
4283:Agents
4151:(MeSH)
4125:
4086:
4076:
4037:
3996:
3955:
3916:131895
3914:
3906:
3871:
3864:149146
3861:
3822:
3794:Nature
3773:
3732:
3689:
3660:
3628:
3620:
3577:
3567:
3521:
3513:
3477:
3469:
3434:
3416:
3389:
3379:
3335:
3325:
3281:
3271:
3227:
3186:
3178:
3152:Nature
3135:
3094:
3084:
3045:
3037:
2996:
2961:
2920:
2912:
2874:
2825:
2784:
2739:
2729:
2690:
2682:
2646:
2610:
2569:
2528:
2520:
2474:
2464:
2400:
2396:,
2381:
2371:
2331:
2323:
2288:
2280:
2244:
2209:
2174:
2136:
2095:
2051:
2013:
2003:
1995:
1956:
1776:TGFβRI
1739:ACVR1C
1735:ACVR1B
1730:ACVR2B
1710:Noggin
1687:BMPR1B
1683:BMPR1A
1649:TGFβRI
1645:ACVR1B
1640:ACVR2B
1611:ACVR1B
1606:ACVR2A
1574:ACVR1B
1569:ACVR2A
1362:, and
1311:, and
1297:TGF-β3
1293:TGF-β2
1289:TGF-β1
1174:I-SMAD
1136:R-SMAD
1130:SMADs
1115:I-SMAD
1105:R-SMAD
1076:serine
1070:, and
1020:cancer
955:GTPase
945:, and
821:-rich
779:ligand
676:somite
576:Viable
565:Lethal
550:Viable
539:Lethal
528:Lethal
361:ligand
357:kinase
322:Viable
308:Lethal
291:Lethal
277:Lethal
263:Viable
249:Viable
214:retina
161:8 and
98:organs
73:; and
4445:TFIIH
4440:TFIID
4264:Hippo
4244:Notch
3912:S2CID
3626:S2CID
3519:S2CID
3475:S2CID
3184:S2CID
3043:S2CID
2918:S2CID
2688:S2CID
2526:S2CID
2419:with
2329:S2CID
2286:S2CID
1993:JSTOR
1800:THBS1
1796:LTBP1
1791:SMAD4
1786:SMAD3
1782:SMAD2
1766:TGFβs
1759:Lefty
1754:SMAD4
1749:SMAD3
1745:SMAD2
1725:Nodal
1705:SMAD4
1700:SMAD8
1696:SMAD5
1693:SMAD1
1678:BMPR2
1664:SMAD4
1659:SMAD3
1655:SMAD2
1635:GDF11
1626:SMAD4
1621:SMAD3
1617:SMAD2
1589:SMAD4
1584:SMAD3
1580:SMAD2
1500:Nodal
1263:SMAD4
1251:SMAD4
1247:SMAD5
1243:SMAD1
1239:SMAD3
1235:SMAD2
1225:, or
1223:Nodal
1200:SMAD4
1183:SMAD7
1179:SMAD6
1167:SMAD4
1153:SMAD5
1149:SMAD3
1145:SMAD2
1141:SMAD1
1127:Class
1044:TGF-β
908:actin
605:Stat1
573:Stat4
562:Stat3
547:Stat1
4215:GPCR
4123:ISBN
4108:text
4084:PMID
4058:Cell
4035:PMID
3994:PMID
3953:PMID
3904:PMID
3869:PMID
3820:PMID
3771:PMID
3730:PMID
3687:ISBN
3658:ISBN
3618:PMID
3575:PMID
3511:PMID
3467:PMID
3432:PMID
3387:PMID
3333:PMID
3279:PMID
3225:PMID
3176:PMID
3133:PMID
3092:PMID
3035:PMID
2994:PMID
2959:PMID
2910:PMID
2898:2007
2872:PMID
2846:and
2823:PMID
2782:PMID
2764:Cell
2737:PMID
2680:PMID
2664:Cell
2644:PMID
2608:PMID
2590:Cell
2567:PMID
2518:PMID
2472:PMID
2398:PMID
2379:PMID
2321:PMID
2278:PMID
2262:Cell
2242:PMID
2207:PMID
2172:PMID
2134:PMID
2093:PMID
2049:PMID
2011:PMID
1954:PMID
1923:2018
1819:and
1601:GDF1
1464:and
1442:and
1432:and
1407:BMP7
1405:and
1403:BMP4
1399:BMP7
1391:BMP4
1387:BMP7
1385:and
1383:BMP4
1326:and
1245:and
1237:and
1192:SMAD
1181:and
1155:and
1054:The
1018:and
997:. IP
910:and
880:GSK3
813:The
662:and
640:The
536:Jak2
525:Jak1
453:the
210:mRNA
181:10.
48:cell
4227:RTK
4222:Wnt
4157:at
4074:PMC
4066:doi
4062:134
4025:doi
4021:279
3984:doi
3943:doi
3939:118
3896:doi
3859:PMC
3851:doi
3810:doi
3798:388
3761:doi
3720:doi
3716:115
3610:doi
3598:296
3565:PMC
3555:doi
3503:doi
3459:doi
3455:129
3424:doi
3377:PMC
3369:doi
3323:PMC
3315:doi
3269:PMC
3261:doi
3257:329
3215:doi
3168:doi
3156:411
3123:doi
3082:PMC
3074:doi
3070:170
3025:doi
3021:140
2986:doi
2949:doi
2902:doi
2862:doi
2858:172
2848:Bmp
2813:doi
2772:doi
2768:107
2727:PMC
2719:doi
2715:119
2672:doi
2636:doi
2598:doi
2594:109
2557:doi
2553:117
2510:doi
2498:296
2462:PMC
2454:doi
2450:351
2390:doi
2369:PMC
2361:doi
2357:115
2313:doi
2270:doi
2234:doi
2199:doi
2164:doi
2124:doi
2120:130
2083:doi
2079:271
2041:doi
2001:PMC
1985:doi
1981:109
1946:doi
1718:DAN
1379:BMP
1036:TGF
884:APC
751:PKA
695:IHH
683:DHH
672:SHH
601:Fgf
485:),
397:Ras
391:An
317:Fgf
303:Fgf
286:Fgf
272:Fgf
258:Fgf
244:Fgf
206:fgf
199:Fgf
195:Fgf
191:Fgf
183:Fgf
179:Fgf
171:Tbx
163:Fgf
159:Fgf
111:Wnt
30:In
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