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MyD88. IRAK-1 binding to MyD88 brings it into close proximity with IRAK-4 so that IRAK-4 can phosphorylate and activate IRAK-1. Once phosphorylated, IRAK-1 recruits the adaptor protein TNF receptor associated factor 6 (TRAF6) and the IRAK-1-TRAF6 complex dissociates from the IL-1R complex. The IRAK-1-TRAF6 complex interacts with a pre-existing complex at the plasma membrane consisting of TGF-β activated kinase 1 (TAK1), and two TAK binding proteins, TAB1 and TAB2. TAK1 is a mitogen-activated protein kinase kinase kinase (MAPKKK). This interaction leads to the phosphorylation of TAB2 and TAK1, which then translocate to the cytosol with TRAF6 and TAB1. IRAK-1 remains at the membrane and is targeted for degradation by ubiquitination. Once the TAK1-TRAF6-TAB1-TAB2 complex is in the cytosol, ubiquitination of TRAF6 in triggers the activation of TAK1 kinase activity. TAK1 can then activate two transcription pathways, the nuclear factor-κB (NF-κB) pathway and the mitogen-activated protein kinase (MAPK) pathway. To activate the NF-κB pathway, TAK1 phosphorylates the IκB kinase (IKK) complex, which subsequently phosphorylates the NF-κB inhibitor, IκB, targeting it for degradation by the proteasome. Once IκB is removed, the NF-κB proteins p65 and p50 are free to translocate into the nucleus and activate transcription of proinflammatory genes. To activate the MAPK pathway, TAK1 phosphorylates MAPK kinase (MKK) 3/4/6, which then phosphorylate members of the MAPK family, c-Jun N-terminal kinase (JNK) and p38. Phosphorylated JNK/p38 can then translocate into the nucleus and phosphorylate and activate transcription factors such as c-Fos and c-Jun.
190:
TLR9 mediated IFN-α induction requires the formation of a complex consisting of MyD88, TRAF6 and the interferon regulatory factor 7 (IRF7). IRF7 is a transcription factor that translocates into the nucleus when activated and initiates transcription of IFN-α. IRAK-1 was shown to directly phosphorylates IRF7 in vitro and the kinase activity of IRAK-1 was shown to be essential for IRF7 transcriptional activation. It was subsequently shown that IRAK-1 is required for the activation of interferon regulatory factor 5 (IRF5). IRF5 is another transcription factor that induces IFN production following stimulation of TLR7, TLR8 and TLR9 by specific viruses. In order to be activated, IRF5 must be polyubiquitinated by TRAF6. It has been shown that TRAF6-mediated ubiquitination of IRF5 is dependent on the kinase activity of IRAK-1.
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and MAPK signaling. It has also been shown that IRAK-M negatively regulates the alternative NF-κB pathway in TLR2 signaling. The alternative NF-κB pathway is predominantly triggered by CD40, lymphotoxin β receptor (LT), and the B-cell activating receptor belonging to the TNF family (BAFF receptor). The alternative NF-κB pathway involves the activation of NF-κN-inducing kinase (NIK) and subsequent phosphorylation of the transcription factors p100/RelB in an IKKα-dependent mechanism. It was observed that IRAK-M knockout resulted in increased induction of the alternative NF-κB pathway but not the classical pathway. The mechanism by which IRAK-M inhibits NF-κB signaling is still unknown.
123:, that functions downstream of a Toll receptor. Cao's lab confirmed the kinase's activity as necessarily associated with the IL-1 receptor by immunoprecipitating the IL-1 receptors from different cell types treated with IL-1 and without IL-1. Even cells without over-expressed IL-1 receptors showed kinase activity when exposed to IL-1, and were able to co-precipitate a protein kinase with endogenous IL-1 receptors. Thus the human IL-1 receptor's accessory protein was named Interleukin-1 Receptor-Associated Kinase.
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metastasis. In tumour cells containing the L265P MyD88 mutant, protein-signalling complexes spontaneously assemble, activating IRAK-4's kinase activity and promoting inflammation and growth independent of
Interleukin-1 signalling. IRAK-4 inhibiting drugs are thus a potential therapeutic treatment for lymphoid malignancies with the L265P MyD88 mutation, especially in Waldenström's Macroglobulinaemia, in which BTK and IRAK1/4 inhibitors have shown promising but unconfirmed results.
141:
KD is responsible for the kinase activity of IRAK proteins and consists of 12 subdomains. All IRAK KDs have an ATP binding pocket with an invariable lysine residue in subdomain II, however, only IRAK-1 and IRAK-4 have an aspartate residue in the catalytic site of subdomain VI, which is thought to be critical for kinase activity. It is thought that IRAK-2 and IRAK-M are catalytically inactive because they lack this aspartate residue in the KD.
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such as, bacterial lipopolysaccharide (LPS), viral double-stranded RNA, etc. TLRs are similar to IL-1Rs in that they do not possess intrinsic kinase activity and require adaptor molecules to relay their signals. Stimulation of TLRs can also result in NF-κB and MAPK mediated transcription, similar to the IL-1R signaling pathway.
51:. This is followed by the activation of IRAKs. TLRs and IL-1R members have a highly conserved amino acid sequence in their cytoplasmic domain called the Toll/Interleukin-1 (TIR) domain. The elicitation of different TLRs/IL-1Rs results in similar signaling cascades due to their homologous TIR motif leading to the activation of
35:) family plays a crucial role in the protective response to pathogens introduced into the human body by inducing acute inflammation followed by additional adaptive immune responses. IRAKs are essential components of the Interleukin-1 receptor signaling pathway and some Toll-like receptor signaling pathways.
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It has been shown that IRAK-1 is essential for TLR7 and TLR9 interferon (IFN) induction. TLR7 and TLR9 in plasmacytoid dendritic cells (pDCs) recognize viral nucleic acids and trigger the production of interferon-α (IFN-α), an important cytokine for inducing an antiviral state in host cells. TLR7 and
176:
IL-1 binding to IL-1R complex triggers the recruitment of the adaptor molecule MyD88 through interactions with the TIR domain. MyD88 brings IRAK-4 to the receptor complex. Preformed complexes of the adaptor molecule Tollip and IRAK-1 are also recruited to the receptor complex, allowing IRAK-1 to bind
172:
Interleukin-1 receptors (IL-1Rs) are cytokine receptors that transduce an intracellular signaling cascade in response to the binding of the inflammatory cytokine interleukin-1 (IL-1). This signaling cascade results in the initiation of transcription of certain genes involved in inflammation. Because
240:
Mutations in the gene for IRAK-M have been identified as contributors to early onset asthma. Compromised IRAK-M leads to overproduction of inflammatory cytokines in the lungs, eventually triggering T cell mediated allergic reactions and exacerbation of asthma symptoms. Researchers have proposed that
201:
One of the most distinct features of IRAK-M is that it is a negative regulator of TLR signaling to prevent excessive inflammation. It is thought that IRAK-M enhances the binding of MyD88 to IRAK-1 and IRAK-4, preventing IRAK-1 from dissociating from the receptor complex and inducing downstream NF-κB
236:
Autoimmune disorders such as MS, rheumatoid arthritis, lupus and psoriasis are caused by innate immune system deregulation inducing chronic inflammation. In most cases, inhibition of IRAK-1 and IRAK-4 are suspected to the most effective targets for knockout drugs, as their functions are integral to
205:
IRAK-4 is an essential component of MyD88 mediated signaling pathways and is therefore critical for both IL-1R and TLR signaling. MyD88 acts as a scaffold protein for the interaction between IRAK-1 and IRAK-4, allowing IRAK-4 to phosphorylate IRAK-1, leading to autophosphorylation and activation of
197:
IRAK-2 plays an important role in TLR-mediated NF-κB activation. Knocking down IRAK-2 has been shown to impair NF-κB activation by TLR3, TLR4 and TLR8. The mechanism of how IRAK-2 functions is still unknown, however, IRAK-2 has been shown to interact with a TIR adaptor protein that does not bind to
193:
IRAK-1 has also been shown to play a critical role in TLR4 interleukin-10 (IL-10) induction. TLR4 recognizes bacterial LPS and triggers the transcription of IL-10, a cytokine regulating the inflammatory response. IL-10 transcription is activated by signal transducer and activator of transcription 3
185:
Toll-like receptors (TLRs) are important innate immune receptors that recognize pathogen associated molecular patterns (PAMPs) and initiate the appropriate immune response to eliminate a particular pathogen. PAMPs are conserved motifs associated with microorganisms that are not found in host cells,
150:
IRAK-1 contains a region that is rich in serine, proline, and threonine (proST). It is thought that IRAK-1 undergoes hyperphosphorylation in this region. The proST region also contains two proline (P), glutamic acid (E), serine (S) and threonine (T)-rich (PEST) sequences that are thought to promote
140:
All IRAK family members are multidomain proteins consisting of a conserved N-terminal Death Domain (DD) and a central kinase domain (KD). The DD is a protein interaction motif that important for interacting with other signaling molecules such as the adaptor protein MyD88 and other IRAK members. The
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Yang, Kun; Puel, Anne; Zhang, Shenying; Eidenschenk, Céline; Ku, Cheng-Lung; Casrouge, Armanda; Picard, Capucine; von
Bernuth, Horst; Senechal, Brigitte; Plancoulaine, Sabine; Al-Hajjar, Sami; Al-Ghonaium, Abdulaziz; Maródi, László; Davidson, Donald; Speert, David; Roifman, Chaim; Garty, Ben-Zion;
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In 1997, MyD88 was identified as the cytosolic protein that recruits IRAKs to the cytosolic domains of IL-1 receptors, mediating IL-1's signal transduction to the cytosolic signal cascade. Subsequent studies associated IRAKs with multiple signalling pathways triggered by interleukin, and specified
1312:
Song, Kyung W; Talamas, Francisco X; Suttmann, Rebecca T; Olson, Pam S; Barnett, Jim W; Lee, Simon W; Thompson, Kelly D; Jin, Sue; Hekmat-Nejad, Mohammad; Cai, Terrence Z; Manning, Anthony M; Hill, Ronald J; Wong, Brian R (2009). "The kinase activities of interleukin-1 receptor associated kinase
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Balaci, Lenuta; Spada, Maria
Cristina; Olla, Nazario; Sole, Gabriella; Loddo, Laura; Anedda, Francesca; Naitza, Silvia; Zuncheddu, Maria Antonietta; Maschio, Andrea; Altea, Daniele; Uda, Manuela; Pilia, Sabrina; Sanna, Serena; Masala, Marco; Crisponi, Laura; Fattori, Matilde; Devoto, Marcella;
105:
The newest described IRAK family member, IRAK-4, has been found to be critical for the recruitment of IRAK-1 and for its activation/degradation. IL-1 stimulates IRAK-4 to the IL-1R complex initiating the Toll/IL-1 receptor signaling cascade upstream of IRAKs, so the deletion of IRAK-1 does not
214:
Interleukin 1 is a cytokine that acts locally and systemically in the innate immune system. IL-1a and IL-1ß are known for causing inflammation, but can also cause induction of other proinflammatory cytokines, and fever. Because IRAKs are a crucial step in the IL-1 receptor signalling pathway,
227:
In 2013, Garrett
Rhyasen and his colleagues at the University of Cincinnati studied the contribution of active IRAK-1 and IRAK-4 in human myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). They found that IRAK1 knockout therapy incited apoptosis and impaired leukemic progenitor
115:
IRAKs were first identified in 1994 by
Michael Martin and colleagues when they successfully co-precipitated a protein kinase with type I interleukin-1 receptors (IL-1RI) from human T cells. They speculated that this kinase was the link between the T cell's transmembrane IL-1 receptor and the
223:
Inflammation signalling is known to be a major factor in many cancer types, and an inflammatory microclimate is a key aspect of human tumours. IL-1ß, which activates the inflammatory signalling pathway containing IRAKs, is directly involved in tumour cell growth, angiogenesis, invasion, and
198:
IRAK-1, called Mal/TIRAP. Mal/TIRAP has been specifically implicated in TLR2 and TLR4 mediated NF-κB signaling. In addition, it has been shown that IRAK-2 is recruited to the TLR3 receptor. IRAK-2 is the only IRAK family member that is known to play a role in TLR3 signaling.
94:
There is some evidence that IRAK-1 functions in regulating other signaling cascades leading to NF-κB activation. One signaling pathway in particular nerve growth factor (NGF) may be dependent on the function of IRAK-1 in its signaling pathway for its activation and cell
67:
of pro-inflammatory genes. Understanding the key players and their roles in the TLR/IL-1R pathway is important because the presence of mutations causing the abnormal regulation of Toll/IL-1R signaling leading to a variety of acute inflammatory and autoimmune diseases.
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The C-terminal domain does not seem to show much similarity between IRAK family members. The C-terminal domain is important for the interaction with the signaling molecule TRAF6. IRAK-1 contains three TRAF6 interaction motifs, IRAK-2 contains two and IRAK-M contains
215:
deficiencies or over-expression of IRAKs can cause suboptimal or overactive cellular response to IL-1a and IL-1ß. Thus
Interleukin-1 Receptor Associated Kinases are promising therapeutic targets for autoimmune-, immunodeficiency-, and cancer-related disorders.
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activity. They also established that IRAK4, while imperative to proliferation of human hematologic malignancies, is not imperative to the pathogenesis of MDS/AML. Further testing of IRAK-inhibitory therapy could prove essential to cancer therapy development.
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Doratiotto, Silvia; Rassu, Stefania; Mereu, Simonetta; Giua, Enrico; Cadeddu, Natalina
Graziella; Atzeni, Roberto; Pelosi, Umberto; Corrias, Adriano; Perra, Roberto; Torrazza, Pier Luigi; Pirina, Pietro; Ginesu, Francesco; et al. (2007).
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Martin, Michael; Böl, Gaby Fleur; Eriksson, Anders; Resch, Klaus; Brigelius-Flohé, Regina (1994). "Interleukin-1-induced activation of a protein kinase co-precipitating with the type I interleukin-1 receptor in T cells".
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Ozinsky, Adrian; Barrat, Franck J; Coffman, Robert L; Miller, Richard L; Li, Xiaoxia; Lebon, Pierre; Rodriguez-Gallego, Carlos; Chapel, Helen; Geissmann, Frédéric; Jouanguy, Emmanuelle; Casanova, Jean-Laurent (2005).
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Uematsu, Satoshi; Sato, Shintaro; Yamamoto, Masahiro; Hirotani, Tomonori; Kato, Hiroki; Takeshita, Fumihiko; Matsuda, Michiyuki; Coban, Cevayir; Ishii, Ken J; Kawai, Taro; Takeuchi, Osamu; Akira, Shizuo (2005).
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Bahia, Malkeet Singh; Kaur, Maninder; Silakari, Pragati; Silakari, Om (2015). "Interleukin-1 receptor associated kinase inhibitors: Potential therapeutic agents for inflammatory- and immune-related disorders".
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Kanakaraj, Palanisamy; Schafer, Peter H; Cavender, Druie E; Wu, Ying; Ngo, Karen; Grealish, Patrick F; Wadsworth, Scott A; Peterson, Per A; Siekierka, John J; Harris, Crafford A; Fung-Leung, Wai-Ping (1998).
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Bahia MS., Kaur M., Silakari P, Silakari O. 2015. Interleukin-1 receptor associated kinase inhibitors: Potential therapeutic agents for inflammatory- and immune-related disorders. Cell. Sig. 27: 1039-1055
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IRAK-M is specific to monomyeloic cells (monocytes and macrophages) while the other IRAKs that are ubiquitously expressed. IRAK-M negatively regulates TLR signaling by inhibiting the IRAK-4/IRAK-1 complex
98:
IRAK-2 has 4 isoforms IRAK-2a, IRAK-2b, IRAK-2c, and IRAK-2d. The latter two have negative feedback in the TLR signaling pathways. IRAK-2a and IRAK-2b positively activate NF-κB/TLR pathway by stimulating
119:
The name “IRAK” came from
Zhaodan Cao and colleagues in 1995. The DNA sequence analysis of IRAK's domains revealed many conserved amino acids with the serine/threonine specific protein kinase Pelle in
3779:
87:. Two are active kinases, IRAK-1 and IRAK-4, and two are inactive, IRAK-2 and IRAK-M, but all regulate the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways.
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Suzuki, N., Suzuki, S., and Saito, T. 2005. IRAKs: Key
Regulatory Kinases of Innate Immunity. Curr. Med. Chem. – Anti-Inflammatory & Anti-Allergy Agents, 4(1), 13-20.
194:(STAT3). IRAK-1 forms a complex with STAT3 and the IL-10 promoter element in the nucleus and is required for STAT3 phosphorylation and activation of IL-10 transcription.
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Schoenemeyer, Annett; Barnes, Betsy J; Mancl, Margo. E; Latz, Eicke; Goutagny, Nadege; Pitha, Paula M; Fitzgerald, Katherine A; Golenbock, Douglas T (2005).
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476:"Identification of Interleukin 1 Receptor-associated Kinase as a Conserved Component in the p75-Neurotrophin Receptor Activation of Nuclear Factor-κB"
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respond the interleukin-1 (IL-1) family cytokines. These receptors initiate an intracellular signaling cascade through adaptor proteins, primarily,
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803:"Interleukin (IL)-1 Receptor–associated Kinase (IRAK) Requirement for Optimal Induction of Multiple IL-1 Signaling Pathways and IL-6 Production"
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IL-1Rs do not possess intrinsic kinase activity, they rely on the recruitment of adaptor molecules, such as IRAKs, to transduce their signals.
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874:"Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-α induction"
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Rhyasen GW., Bolanos L., Starczynowski DT. 2013. Differential IRAK signaling in hematologic malignancies. Exp. Hematology. 41: 1005-1007.
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IRAK-1 . IRAK-4 is critical for IL-1R and TLR NF-κB and MAPK signaling pathways as well as TLR7/9 MyD88-mediated interferon activation.
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Flannery, S., & Bowie, A. G. (1215). The interleukin-1 receptor-associated kinases: Critical regulators of innate immune signalling
517:"Lipopolysaccharide (LPS)-induced Macrophage Activation and Signal Transduction in the Absence of Src-Family Kinases Hck, Fgr, and Lyn"
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1107:"Human TLR-7-, -8-, and -9-Mediated Induction of IFN-α/β and -λ is IRAK-4 Dependent and Redundant for Protective Immunity to Viruses"
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1057:"The involvement of the interleukin-1 receptor-associated kinases (IRAKs) in cellular signaling networks controlling inflammation"
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IRAKs are membrane proximal putative serine-threonine kinases. Four IRAK family members have been described in humans:
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386:"Functional Diversity and Regulation of Different Interleukin-1 Receptor-Associated Kinase (IRAK) Family Members"
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625:"The Role of Interleukin 1 Receptor-associated Kinase-4 (IRAK-4) Kinase Activity in IRAK-4-mediated Signaling"
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1013:"IRAK1 Serves as a Novel Regulator Essential for Lipopolysaccharide-induced Interleukin-10 Gene Expression"
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964:"Functional Regulation of MyD88-Activated Interferon Regulatory Factor 5 by K63-Linked Polyubiquitination"
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Cao, Z; Henzel, W. J; Gao, X (1996). "IRAK: A Kinase
Associated with the Interleukin-1 Receptor".
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1313:(IRAK)-1 and 4 are redundant in the control of inflammatory cytokine expression in human cells".
923:"The Interferon Regulatory Factor, IRF5, is a Central Mediator of Toll-like Receptor 7 Signaling"
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Lye, Elizabeth; Mirtsos, Christine; Suzuki, Nobutaka; Suzuki, Shinobu; Yeh, Wen-Chen (2004).
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Wesche, Holger; Henzel, William J; Shillinglaw, Wendy; Li, Shyun; Cao, Zhaodan (1997).
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1265:"Toll-like receptors as therapeutic targets for autoimmune connective tissue diseases"
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Wang, Zhulun; Wesche, Holger; Stevens, Tracey; Walker, Nigel; Yeh, Wen-Chen (2009).
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566:"IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase"
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326:"Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins"
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increasing IRAK-M function in these individuals may moderate asthma symptoms.
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abolish the activation of NF-κB and mitogen-activated protein kinase pathways.
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1351:"IRAK-M is Involved in the Pathogenesis of Early-Onset Persistent Asthma"
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761:"MyD88: An Adapter That Recruits IRAK to the IL-1 Receptor Complex"
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2132:
2127:
2021:
2016:
2011:
2006:
2001:
1996:
1957:
1889:
1884:
1833:
1828:
1754:
1749:
1744:
1710:
1702:
3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase
1504:
1489:
1484:
1479:
1474:
1469:
163:
84:
80:
76:
72:
48:
286:
Takeda, Kiyoshi; Akira, Shizuo (2004). "TLR signaling pathways".
4463:
4375:
4312:
3020:
2947:
2942:
2932:
2905:
2662:
2612:
2593:
2588:
2583:
2578:
2533:
2528:
2523:
2518:
2465:
2421:
2362:
2357:
2307:
2292:
2262:
2192:
2108:
2103:
2098:
2031:
1933:
1874:
1869:
1773:
1739:
1624:
1619:
1614:
1583:
1551:
1539:
1534:
1529:
1519:
1514:
3545:
3254:
3178:
2554:
1445:
1398:
2989:
1524:
1509:
379:
377:
375:
373:
371:
369:
90:
Some special/significant features of each IRAK family member:
324:
Watters, Tanya M; Kenny, Elaine F; O'Neill, Luke A J (2007).
1263:
Li, Jing; Wang, Xiaohui; Zhang, Fengchun; Yin, Hang (2013).
1050:
1048:
3250:
1011:
Huang, Yingsu; Li, Tao; Sane, David C; Li, Liwu (2004).
854:
852:
850:
848:
846:
3704:
Methoxy polyethylene glycol-epoetin beta (CERA/Mircera)
866:
864:
116:
cytosolic signalling pathway's downstream components.
4622:
237:
the cytokine pathways inducing chronic inflammation.
39:(TLRs) detect microorganisms by recognizing specific
962:
Balkhi, M. Y; Fitzgerald, K. A; Pitha, P. M (2008).
564:
Li, S; Strelow, A; Fontana, E. J; Wesche, H (2002).
4542:
4520:
4462:
4374:
4311:
4294:
4287:
4267:
4247:
4227:
4203:
4162:
3969:
3960:
3915:
3895:
3844:
3778:
3722:
3611:
3602:
3582:
3437:
3401:
3370:
3339:
3288:
3192:
3090:
3073:
3056:
3039:
3010:
2870:
2770:
2711:
2602:
2568:
2508:
2484:
2445:
2411:
2117:
2088:
2064:
2045:
1966:
1942:
1903:
1859:
1842:
1818:
1782:
1763:
1729:
1700:
1633:
1599:
1459:
474:Mamidipudi, V.; Li, X.; Wooten, M. W. J. (2002).
3796:Granulocyte macrophage colony-stimulating factor
29:interleukin-1 receptor (IL-1R) associated kinase
570:Proceedings of the National Academy of Sciences
3557:
3266:
1461:Non-specific serine/threonine protein kinases
1410:
8:
4563:Leukemia/leukocyte inhibitory factor (LIF)
4308:
4291:
3966:
3608:
3564:
3550:
3542:
3273:
3259:
3251:
3189:
3175:
2565:
2551:
1844:Goodpasture-antigen-binding protein kinase
1456:
1442:
1417:
1403:
1395:
515:Meng, Fanying; Lowell, Clifford A (1997).
4558:FMS-like tyrosine kinase 3 ligand (FLT3L)
3987:Interferon alpha (interferon alfa, IFN-α)
2557:Serine/threonine-specific protein kinases
1731:(isocitrate dehydrogenase (NADP+)) kinase
1448:Serine/threonine-specific protein kinases
1430:Serine/threonine-specific protein kinases
1374:
1288:
1227:
1202:Rhyasen, G W; Starczynowski, D T (2014).
1130:
1080:
1028:
987:
938:
897:
826:
776:
640:
599:
589:
540:
491:
450:
401:
341:
260:at the U.S. National Library of Medicine
258:Interleukin-1 Receptor-Associated Kinases
4580:Additional cytokine receptor modulators:
3092:Receptor protein serine/threonine kinase
384:Janssens, Sophie; Beyaert, Rudi (2003).
18:Interleukin-1 receptor-associated kinase
4629:
3075:Low-density-lipoprotein receptor kinase
250:
65:AP-1-dependent transcriptional response
4404:Cucurbitacin I (elatericin B, JSI-124)
1355:The American Journal of Human Genetics
41:pathogen-associated molecular patterns
3740:Granulocyte colony-stimulating factor
1820:Fas-activated serine/threonine kinase
431:Current Topics in Medicinal Chemistry
7:
4099:Interferon kappa (IFN-ε/κ/τ/ζ, IFNK)
3872:Macrophage colony-stimulating factor
3101:Bone morphogenetic protein receptors
878:The Journal of Experimental Medicine
807:The Journal of Experimental Medicine
521:The Journal of Experimental Medicine
427:"IRAK-4 Inhibitors for Inflammation"
4573:Thymic stromal lymphopoietin (TSLP)
1635:Dephospho-(reductase kinase) kinase
2090:G-protein coupled receptor kinases
1055:Ringwood, Lorna; Li, Liwu (2008).
25:
2080:Beta adrenergic receptor kinase-2
1765:(tyrosine 3-monooxygenase) kinase
59:(IKK) complex, which initiates a
53:mitogen-activated protein kinases
4632:
2772:Mitogen-activated protein kinase
1281:10.1016/j.pharmthera.2013.03.003
160:Interleukin-1 receptor signaling
4104:Interferon omega (IFN-ω, IFNW1)
3158:Anti-Müllerian hormone receptor
3041:(acetyl-CoA carboxylase) kinase
2713:(RNA-polymerase)-subunit kinase
2075:Beta adrenergic receptor kinase
2066:Beta adrenergic receptor kinase
1269:Pharmacology & Therapeutics
1017:Journal of Biological Chemistry
927:Journal of Biological Chemistry
629:Journal of Biological Chemistry
2781:Extracellular signal-regulated
968:Molecular and Cellular Biology
667:European Journal of Immunology
1:
2845:P38 mitogen-activated protein
1944:cGMP-dependent protein kinase
1905:cAMP-dependent protein kinase
1601:Pyruvate dehydrogenase kinase
1547:Ataxia telangiectasia mutated
1169:10.1016/j.cellsig.2015.02.025
778:10.1016/S1074-7613(00)80402-1
730:10.1126/science.271.5252.1128
403:10.1016/S1097-2765(03)00053-4
1644:AMP-activated protein kinase
1327:10.1016/j.molimm.2008.12.012
1123:10.1016/j.immuni.2005.09.016
181:Toll-like receptor signaling
3948:Thrombopoietin (THPO, MGDF)
3714:Pegol sihematide (EPO-018B)
3634:Carbamylated erythropoietin
2559:(EC 2.7.11.21-EC 2.7.11.30)
1204:"IRAK signalling in cancer"
330:Immunology and Cell Biology
151:the degradation of IRAK-1.
4676:
2486:Elongation factor 2 kinase
1450:(EC 2.7.11.1-EC 2.7.11.20)
1073:10.1016/j.cyto.2007.12.012
443:10.2174/156802609789044407
300:10.1016/j.smim.2003.10.003
4497:Tofacitinib (tasocitinib)
4454:Tofacitinib (tasocitinib)
4361:Tofacitinib (tasocitinib)
3429:Michaelis–Menten kinetics
3188:
3174:
2881:MAP kinase kinase kinases
2564:
2550:
2413:Myosin light-chain kinase
2119:Ca2+/calmodulin-dependent
1784:Myosin-heavy-chain kinase
1455:
1441:
1208:British Journal of Cancer
4175:Interferon gamma (IFN-γ)
3321:Diffusion-limited enzyme
3181:Dual-specificity kinases
262:Medical Subject Headings
155:Role in immune signaling
4075:Interferon beta (IFN-β)
2604:Cyclin-dependent kinase
819:10.1084/jem.187.12.2073
168:IL-1R Signaling pathway
4553:Cardiotrophin 1 (CT-1)
1030:10.1074/jbc.M410369200
940:10.1074/jbc.M412584200
679:10.1002/eji.1830240717
642:10.1074/jbc.M402666200
591:10.1073/pnas.082100399
533:10.1084/jem.185.9.1661
493:10.1074/jbc.m109730200
343:10.1038/sj.icb.7100095
288:Seminars in Immunology
169:
4550:Additional cytokines:
4477:Decernotinib (VX-509)
4114:Peginterferon alfa-2b
4109:Peginterferon alfa-2a
3629:Asialo erythropoietin
3414:Eadie–Hofstee diagram
3347:Allosteric regulation
167:
127:multiple IRAK types.
4065:Interferon alfacon-1
3694:Erythropoietin (EPO)
3424:Lineweaver–Burk plot
2447:Phosphorylase kinase
1315:Molecular Immunology
1220:10.1038/bjc.2014.513
980:10.1128/MCB.00662-08
890:10.1084/jem.20042372
232:Autoimmune Disorders
45:IL-1R family members
4212:See IL-28R (IFNLR)
4180:Interferon gamma 1b
4070:Interferon alpha-n3
1157:Cellular Signalling
1023:(49): 51697–52303.
933:(17): 17005–17012.
722:1996Sci...271.1128C
716:(5252): 1128–1131.
635:(39): 40653–40658.
582:2002PNAS...99.5567L
486:(31): 28010–28018.
37:Toll-like receptors
4568:Oncostatin M (OSM)
4094:Interferon beta 1b
4089:Interferon beta 1a
4060:Interferon alfa n1
4055:Interferon alfa 2b
4050:Interferon alfa 2a
3884:Kinase inhibitors:
3383:Enzyme superfamily
3316:Enzyme promiscuity
3058:Tropomyosin kinase
3012:Tau-protein kinase
170:
136:Functional domains
4620:
4619:
4616:
4615:
4538:
4537:
4305:
4223:
4222:
3956:
3955:
3699:Erythropoietin-Fc
3573:Cytokine receptor
3539:
3538:
3248:
3247:
3244:
3243:
3240:
3239:
3170:
3169:
3166:
3165:
2546:
2545:
2542:
2541:
2027:Protein kinase N1
1982:Protein kinase Cζ
974:(24): 7296–7508.
813:(12): 2073–2079.
61:nuclear factor-κB
16:(Redirected from
4667:
4637:
4636:
4628:
4309:
4299:
4292:
4151:Decoy receptors:
3967:
3644:Darbepoetin alfa
3609:
3566:
3559:
3552:
3543:
3419:Hanes–Woolf plot
3362:Enzyme activator
3357:Enzyme inhibitor
3331:Enzyme catalysis
3275:
3268:
3261:
3252:
3190:
3176:
2823:C-Jun N-terminal
2566:
2552:
2056:Rhodopsin kinase
2047:Rhodopsin kinase
1977:Protein kinase C
1968:Protein kinase C
1953:Protein kinase G
1914:Protein kinase A
1525:Protein kinase B
1457:
1443:
1419:
1412:
1405:
1396:
1389:
1388:
1378:
1361:(6): 1103–1114.
1345:
1339:
1338:
1321:(7): 1458–1466.
1309:
1303:
1302:
1292:
1260:
1254:
1251:
1242:
1241:
1231:
1199:
1190:
1187:
1181:
1180:
1163:(6): 1039–1055.
1151:
1145:
1144:
1134:
1101:
1095:
1094:
1084:
1052:
1043:
1042:
1032:
1008:
1002:
1001:
991:
959:
953:
952:
942:
918:
912:
911:
901:
868:
859:
856:
841:
840:
830:
797:
791:
790:
780:
756:
750:
749:
705:
699:
698:
673:(7): 1566–1571.
661:
655:
654:
644:
620:
614:
613:
603:
593:
576:(8): 5567–5572.
561:
555:
554:
544:
527:(9): 1661–1670.
512:
506:
505:
495:
471:
465:
464:
454:
422:
416:
415:
405:
381:
364:
363:
345:
321:
312:
311:
283:
277:
274:
265:
255:
55:(MAPKs) and the
21:
4675:
4674:
4670:
4669:
4668:
4666:
4665:
4664:
4645:
4644:
4643:
4631:
4623:
4621:
4612:
4534:
4530:Deucravacitinib
4516:
4458:
4370:
4298:
4283:
4263:
4243:
4219:
4199:
4158:
3992:Interferon alfa
3952:
3911:
3891:
3840:
3774:
3770:Pegnartograstim
3755:Lipegfilgrastim
3718:
3664:Epoetin epsilon
3598:
3578:
3570:
3540:
3535:
3447:Oxidoreductases
3433:
3409:Enzyme kinetics
3397:
3393:List of enzymes
3366:
3335:
3306:Catalytic triad
3284:
3279:
3249:
3236:
3184:
3162:
3086:
3069:
3052:
3035:
3006:
2866:
2766:
2737:P70-S6 Kinase 1
2707:
2598:
2560:
2538:
2504:
2480:
2441:
2407:
2113:
2084:
2060:
2041:
1962:
1938:
1899:
1855:
1838:
1814:
1808:Aurora C kinase
1803:Aurora B kinase
1798:Aurora A kinase
1778:
1759:
1725:
1696:
1629:
1595:
1451:
1437:
1423:
1393:
1392:
1347:
1346:
1342:
1311:
1310:
1306:
1262:
1261:
1257:
1252:
1245:
1201:
1200:
1193:
1188:
1184:
1153:
1152:
1148:
1103:
1102:
1098:
1054:
1053:
1046:
1010:
1009:
1005:
961:
960:
956:
920:
919:
915:
870:
869:
862:
857:
844:
799:
798:
794:
758:
757:
753:
707:
706:
702:
663:
662:
658:
622:
621:
617:
563:
562:
558:
514:
513:
509:
473:
472:
468:
424:
423:
419:
383:
382:
367:
323:
322:
315:
285:
284:
280:
275:
268:
256:
252:
247:
234:
221:
212:
210:Role in disease
183:
162:
157:
138:
133:
113:
23:
22:
15:
12:
11:
5:
4673:
4671:
4663:
4662:
4657:
4647:
4646:
4642:
4641:
4618:
4617:
4614:
4613:
4611:
4610:
4605:
4600:
4595:
4590:
4585:
4576:
4575:
4570:
4565:
4560:
4555:
4546:
4544:
4540:
4539:
4536:
4535:
4533:
4532:
4526:
4524:
4518:
4517:
4515:
4514:
4509:
4504:
4499:
4494:
4489:
4484:
4479:
4474:
4472:Cercosporamide
4468:
4466:
4460:
4459:
4457:
4456:
4451:
4446:
4441:
4436:
4431:
4426:
4421:
4416:
4414:Deuruxolitinib
4411:
4406:
4401:
4396:
4391:
4386:
4380:
4378:
4372:
4371:
4369:
4368:
4363:
4358:
4353:
4348:
4343:
4338:
4333:
4331:Deuruxolitinib
4328:
4323:
4317:
4315:
4306:
4289:
4285:
4284:
4282:
4281:
4273:
4271:
4265:
4264:
4262:
4261:
4253:
4251:
4245:
4244:
4242:
4241:
4233:
4231:
4225:
4224:
4221:
4220:
4218:
4217:
4209:
4207:
4205:IFNLR (λ, III)
4201:
4200:
4198:
4197:
4192:
4183:
4182:
4177:
4168:
4166:
4160:
4159:
4157:
4156:
4147:
4146:
4141:
4136:
4131:
4126:
4117:
4116:
4111:
4106:
4101:
4096:
4091:
4086:
4072:
4067:
4062:
4057:
4052:
4047:
3989:
3984:
3975:
3973:
3971:IFNAR (α/β, I)
3964:
3958:
3957:
3954:
3953:
3951:
3950:
3945:
3940:
3938:Promegapoietin
3935:
3930:
3921:
3919:
3917:Thrombopoietin
3913:
3912:
3910:
3909:
3901:
3899:
3893:
3892:
3890:
3889:
3880:
3879:
3874:
3869:
3864:
3862:Interleukin-34
3859:
3850:
3848:
3842:
3841:
3839:
3838:
3833:
3828:
3819:
3818:
3813:
3808:
3803:
3798:
3793:
3784:
3782:
3776:
3775:
3773:
3772:
3767:
3762:
3757:
3752:
3747:
3742:
3737:
3728:
3726:
3720:
3719:
3717:
3716:
3711:
3706:
3701:
3696:
3691:
3686:
3681:
3676:
3671:
3666:
3661:
3656:
3651:
3646:
3641:
3636:
3631:
3626:
3617:
3615:
3613:Erythropoietin
3606:
3600:
3599:
3597:
3596:
3588:
3586:
3580:
3579:
3571:
3569:
3568:
3561:
3554:
3546:
3537:
3536:
3534:
3533:
3520:
3507:
3494:
3481:
3468:
3455:
3441:
3439:
3435:
3434:
3432:
3431:
3426:
3421:
3416:
3411:
3405:
3403:
3399:
3398:
3396:
3395:
3390:
3385:
3380:
3374:
3372:
3371:Classification
3368:
3367:
3365:
3364:
3359:
3354:
3349:
3343:
3341:
3337:
3336:
3334:
3333:
3328:
3323:
3318:
3313:
3308:
3303:
3298:
3292:
3290:
3286:
3285:
3280:
3278:
3277:
3270:
3263:
3255:
3246:
3245:
3242:
3241:
3238:
3237:
3235:
3234:
3229:
3224:
3219:
3214:
3209:
3204:
3198:
3196:
3186:
3185:
3179:
3172:
3171:
3168:
3167:
3164:
3163:
3161:
3160:
3155:
3150:
3145:
3140:
3135:
3130:
3125:
3124:
3123:
3118:
3113:
3108:
3097:
3095:
3094:(EC 2.7.11.30)
3088:
3087:
3085:
3084:
3080:
3078:
3077:(EC 2.7.11.29)
3071:
3070:
3068:
3067:
3063:
3061:
3060:(EC 2.7.11.28)
3054:
3053:
3051:
3050:
3046:
3044:
3043:(EC 2.7.11.27)
3037:
3036:
3034:
3033:
3028:
3023:
3017:
3015:
3014:(EC 2.7.11.26)
3008:
3007:
3005:
3004:
2999:
2994:
2993:
2992:
2987:
2982:
2977:
2972:
2967:
2962:
2952:
2951:
2950:
2945:
2940:
2935:
2925:
2924:
2923:
2918:
2913:
2908:
2903:
2898:
2893:
2888:
2877:
2875:
2874:(EC 2.7.11.25)
2868:
2867:
2865:
2864:
2863:
2862:
2857:
2852:
2842:
2841:
2840:
2835:
2830:
2820:
2819:
2818:
2813:
2808:
2803:
2798:
2793:
2788:
2777:
2775:
2774:(EC 2.7.11.24)
2768:
2767:
2765:
2764:
2759:
2754:
2749:
2744:
2739:
2734:
2729:
2724:
2718:
2716:
2715:(EC 2.7.11.23)
2709:
2708:
2706:
2705:
2700:
2695:
2690:
2685:
2680:
2675:
2670:
2665:
2660:
2655:
2650:
2645:
2640:
2635:
2630:
2625:
2620:
2615:
2609:
2607:
2606:(EC 2.7.11.22)
2600:
2599:
2597:
2596:
2591:
2586:
2581:
2575:
2573:
2572:(EC 2.7.11.21)
2562:
2561:
2555:
2548:
2547:
2544:
2543:
2540:
2539:
2537:
2536:
2531:
2526:
2521:
2515:
2513:
2512:(EC 2.7.11.21)
2506:
2505:
2503:
2502:
2497:
2491:
2489:
2488:(EC 2.7.11.20)
2482:
2481:
2479:
2478:
2473:
2468:
2463:
2458:
2452:
2450:
2449:(EC 2.7.11.19)
2443:
2442:
2440:
2439:
2434:
2429:
2424:
2418:
2416:
2415:(EC 2.7.11.18)
2409:
2408:
2406:
2405:
2400:
2395:
2390:
2385:
2380:
2375:
2370:
2365:
2360:
2355:
2350:
2345:
2340:
2335:
2330:
2325:
2320:
2315:
2310:
2305:
2300:
2295:
2290:
2285:
2280:
2275:
2270:
2265:
2260:
2255:
2250:
2245:
2240:
2235:
2230:
2225:
2220:
2215:
2210:
2205:
2200:
2195:
2190:
2185:
2180:
2175:
2170:
2165:
2160:
2155:
2150:
2145:
2140:
2135:
2130:
2124:
2122:
2121:(EC 2.7.11.17)
2115:
2114:
2112:
2111:
2106:
2101:
2095:
2093:
2092:(EC 2.7.11.16)
2086:
2085:
2083:
2082:
2077:
2071:
2069:
2068:(EC 2.7.11.15)
2062:
2061:
2059:
2058:
2052:
2050:
2049:(EC 2.7.11.14)
2043:
2042:
2040:
2039:
2034:
2029:
2024:
2019:
2014:
2009:
2004:
1999:
1994:
1989:
1984:
1979:
1973:
1971:
1970:(EC 2.7.11.13)
1964:
1963:
1961:
1960:
1955:
1949:
1947:
1946:(EC 2.7.11.12)
1940:
1939:
1937:
1936:
1931:
1926:
1921:
1916:
1910:
1908:
1907:(EC 2.7.11.11)
1901:
1900:
1898:
1897:
1892:
1887:
1882:
1877:
1872:
1866:
1864:
1863:(EC 2.7.11.10)
1857:
1856:
1854:
1853:
1849:
1847:
1840:
1839:
1837:
1836:
1831:
1825:
1823:
1816:
1815:
1813:
1812:
1811:
1810:
1805:
1800:
1789:
1787:
1780:
1779:
1777:
1776:
1770:
1768:
1761:
1760:
1758:
1757:
1752:
1747:
1742:
1736:
1734:
1727:
1726:
1724:
1723:
1718:
1713:
1707:
1705:
1698:
1697:
1695:
1694:
1693:
1692:
1687:
1682:
1674:
1673:
1672:
1667:
1659:
1658:
1657:
1652:
1640:
1638:
1631:
1630:
1628:
1627:
1622:
1617:
1612:
1606:
1604:
1597:
1596:
1594:
1593:
1592:
1591:
1581:
1580:
1579:
1574:
1569:
1564:
1554:
1549:
1544:
1543:
1542:
1537:
1532:
1522:
1517:
1512:
1507:
1502:
1497:
1492:
1487:
1482:
1477:
1472:
1466:
1464:
1453:
1452:
1446:
1439:
1438:
1424:
1422:
1421:
1414:
1407:
1399:
1391:
1390:
1367:10.1086/518259
1340:
1304:
1275:(3): 441–451.
1255:
1243:
1214:(2): 232–237.
1191:
1182:
1146:
1117:(5): 465–478.
1096:
1044:
1003:
954:
913:
884:(6): 915–923.
860:
842:
792:
771:(6): 837–847.
751:
700:
656:
615:
556:
507:
466:
437:(8): 724–737.
417:
396:(2): 293–302.
390:Molecular Cell
365:
336:(6): 411–419.
313:
278:
266:
249:
248:
246:
243:
233:
230:
220:
217:
211:
208:
182:
179:
161:
158:
156:
153:
148:
147:
137:
134:
132:
129:
112:
109:
108:
107:
103:
100:
96:
24:
14:
13:
10:
9:
6:
4:
3:
2:
4672:
4661:
4658:
4656:
4653:
4652:
4650:
4640:
4635:
4630:
4626:
4609:
4606:
4604:
4601:
4599:
4596:
4594:
4591:
4589:
4586:
4584:
4581:
4578:
4577:
4574:
4571:
4569:
4566:
4564:
4561:
4559:
4556:
4554:
4551:
4548:
4547:
4545:
4541:
4531:
4528:
4527:
4525:
4523:
4519:
4513:
4510:
4508:
4505:
4503:
4500:
4498:
4495:
4493:
4490:
4488:
4485:
4483:
4480:
4478:
4475:
4473:
4470:
4469:
4467:
4465:
4461:
4455:
4452:
4450:
4447:
4445:
4442:
4440:
4437:
4435:
4432:
4430:
4427:
4425:
4422:
4420:
4417:
4415:
4412:
4410:
4407:
4405:
4402:
4400:
4397:
4395:
4392:
4390:
4387:
4385:
4382:
4381:
4379:
4377:
4373:
4367:
4364:
4362:
4359:
4357:
4354:
4352:
4349:
4347:
4344:
4342:
4339:
4337:
4334:
4332:
4329:
4327:
4324:
4322:
4319:
4318:
4316:
4314:
4310:
4307:
4303:
4297:
4293:
4290:
4286:
4279:
4275:
4274:
4272:
4270:
4266:
4259:
4255:
4254:
4252:
4250:
4246:
4239:
4235:
4234:
4232:
4230:
4226:
4215:
4211:
4210:
4208:
4206:
4202:
4196:
4193:
4191:
4188:
4185:
4184:
4181:
4178:
4176:
4173:
4170:
4169:
4167:
4165:
4164:IFNGR (γ, II)
4161:
4155:
4152:
4149:
4148:
4145:
4142:
4140:
4137:
4135:
4132:
4130:
4127:
4125:
4122:
4119:
4118:
4115:
4112:
4110:
4107:
4105:
4102:
4100:
4097:
4095:
4092:
4090:
4087:
4084:
4080:
4076:
4073:
4071:
4068:
4066:
4063:
4061:
4058:
4056:
4053:
4051:
4048:
4045:
4041:
4037:
4033:
4029:
4025:
4021:
4017:
4013:
4009:
4005:
4001:
3997:
3993:
3990:
3988:
3985:
3983:
3982:Albinterferon
3980:
3977:
3976:
3974:
3972:
3968:
3965:
3963:
3959:
3949:
3946:
3944:
3941:
3939:
3936:
3934:
3931:
3929:
3926:
3923:
3922:
3920:
3918:
3914:
3907:
3903:
3902:
3900:
3898:
3894:
3888:
3885:
3882:
3881:
3878:
3875:
3873:
3870:
3868:
3865:
3863:
3860:
3858:
3855:
3852:
3851:
3849:
3847:
3843:
3837:
3834:
3832:
3829:
3827:
3824:
3821:
3820:
3817:
3814:
3812:
3809:
3807:
3804:
3802:
3799:
3797:
3794:
3792:
3789:
3786:
3785:
3783:
3781:
3780:GM-CSF (CSF2)
3777:
3771:
3768:
3766:
3765:Pegfilgrastim
3763:
3761:
3758:
3756:
3753:
3751:
3748:
3746:
3743:
3741:
3738:
3736:
3733:
3730:
3729:
3727:
3725:
3721:
3715:
3712:
3710:
3707:
3705:
3702:
3700:
3697:
3695:
3692:
3690:
3687:
3685:
3684:Epoetin theta
3682:
3680:
3679:Epoetin omega
3677:
3675:
3674:Epoetin kappa
3672:
3670:
3669:Epoetin gamma
3667:
3665:
3662:
3660:
3659:Epoetin delta
3657:
3655:
3652:
3650:
3647:
3645:
3642:
3640:
3637:
3635:
3632:
3630:
3627:
3625:
3622:
3619:
3618:
3616:
3614:
3610:
3607:
3605:
3601:
3594:
3590:
3589:
3587:
3585:
3581:
3577:
3574:
3567:
3562:
3560:
3555:
3553:
3548:
3547:
3544:
3531:
3527:
3526:
3521:
3518:
3514:
3513:
3508:
3505:
3501:
3500:
3495:
3492:
3488:
3487:
3482:
3479:
3475:
3474:
3469:
3466:
3462:
3461:
3456:
3453:
3449:
3448:
3443:
3442:
3440:
3436:
3430:
3427:
3425:
3422:
3420:
3417:
3415:
3412:
3410:
3407:
3406:
3404:
3400:
3394:
3391:
3389:
3388:Enzyme family
3386:
3384:
3381:
3379:
3376:
3375:
3373:
3369:
3363:
3360:
3358:
3355:
3353:
3352:Cooperativity
3350:
3348:
3345:
3344:
3342:
3338:
3332:
3329:
3327:
3324:
3322:
3319:
3317:
3314:
3312:
3311:Oxyanion hole
3309:
3307:
3304:
3302:
3299:
3297:
3294:
3293:
3291:
3287:
3283:
3276:
3271:
3269:
3264:
3262:
3257:
3256:
3253:
3233:
3230:
3228:
3225:
3223:
3220:
3218:
3215:
3213:
3210:
3208:
3205:
3203:
3200:
3199:
3197:
3195:
3191:
3187:
3182:
3177:
3173:
3159:
3156:
3154:
3151:
3149:
3146:
3144:
3141:
3139:
3136:
3134:
3131:
3129:
3126:
3122:
3119:
3117:
3114:
3112:
3109:
3107:
3104:
3103:
3102:
3099:
3098:
3096:
3093:
3089:
3082:
3081:
3079:
3076:
3072:
3065:
3064:
3062:
3059:
3055:
3048:
3047:
3045:
3042:
3038:
3032:
3029:
3027:
3024:
3022:
3019:
3018:
3016:
3013:
3009:
3003:
3000:
2998:
2995:
2991:
2988:
2986:
2983:
2981:
2978:
2976:
2973:
2971:
2968:
2966:
2963:
2961:
2958:
2957:
2956:
2953:
2949:
2946:
2944:
2941:
2939:
2936:
2934:
2931:
2930:
2929:
2926:
2922:
2919:
2917:
2914:
2912:
2909:
2907:
2904:
2902:
2899:
2897:
2894:
2892:
2889:
2887:
2884:
2883:
2882:
2879:
2878:
2876:
2873:
2869:
2861:
2858:
2856:
2853:
2851:
2848:
2847:
2846:
2843:
2839:
2836:
2834:
2831:
2829:
2826:
2825:
2824:
2821:
2817:
2814:
2812:
2809:
2807:
2804:
2802:
2799:
2797:
2794:
2792:
2789:
2787:
2784:
2783:
2782:
2779:
2778:
2776:
2773:
2769:
2763:
2760:
2758:
2755:
2753:
2750:
2748:
2745:
2743:
2740:
2738:
2735:
2733:
2730:
2728:
2725:
2723:
2720:
2719:
2717:
2714:
2710:
2704:
2701:
2699:
2696:
2694:
2691:
2689:
2686:
2684:
2681:
2679:
2676:
2674:
2671:
2669:
2666:
2664:
2661:
2659:
2656:
2654:
2651:
2649:
2646:
2644:
2641:
2639:
2636:
2634:
2631:
2629:
2626:
2624:
2621:
2619:
2616:
2614:
2611:
2610:
2608:
2605:
2601:
2595:
2592:
2590:
2587:
2585:
2582:
2580:
2577:
2576:
2574:
2571:
2567:
2563:
2558:
2553:
2549:
2535:
2532:
2530:
2527:
2525:
2522:
2520:
2517:
2516:
2514:
2511:
2507:
2501:
2498:
2496:
2493:
2492:
2490:
2487:
2483:
2477:
2474:
2472:
2469:
2467:
2464:
2462:
2459:
2457:
2454:
2453:
2451:
2448:
2444:
2438:
2435:
2433:
2430:
2428:
2425:
2423:
2420:
2419:
2417:
2414:
2410:
2404:
2401:
2399:
2396:
2394:
2391:
2389:
2386:
2384:
2381:
2379:
2376:
2374:
2371:
2369:
2366:
2364:
2361:
2359:
2356:
2354:
2351:
2349:
2346:
2344:
2341:
2339:
2336:
2334:
2331:
2329:
2326:
2324:
2321:
2319:
2316:
2314:
2311:
2309:
2306:
2304:
2301:
2299:
2296:
2294:
2291:
2289:
2286:
2284:
2281:
2279:
2276:
2274:
2271:
2269:
2266:
2264:
2261:
2259:
2256:
2254:
2251:
2249:
2246:
2244:
2241:
2239:
2236:
2234:
2231:
2229:
2226:
2224:
2221:
2219:
2216:
2214:
2211:
2209:
2206:
2204:
2201:
2199:
2196:
2194:
2191:
2189:
2186:
2184:
2181:
2179:
2176:
2174:
2171:
2169:
2166:
2164:
2161:
2159:
2156:
2154:
2151:
2149:
2146:
2144:
2141:
2139:
2136:
2134:
2131:
2129:
2126:
2125:
2123:
2120:
2116:
2110:
2107:
2105:
2102:
2100:
2097:
2096:
2094:
2091:
2087:
2081:
2078:
2076:
2073:
2072:
2070:
2067:
2063:
2057:
2054:
2053:
2051:
2048:
2044:
2038:
2035:
2033:
2030:
2028:
2025:
2023:
2020:
2018:
2015:
2013:
2010:
2008:
2005:
2003:
2000:
1998:
1995:
1993:
1990:
1988:
1985:
1983:
1980:
1978:
1975:
1974:
1972:
1969:
1965:
1959:
1956:
1954:
1951:
1950:
1948:
1945:
1941:
1935:
1932:
1930:
1927:
1925:
1922:
1920:
1917:
1915:
1912:
1911:
1909:
1906:
1902:
1896:
1893:
1891:
1888:
1886:
1883:
1881:
1878:
1876:
1873:
1871:
1868:
1867:
1865:
1862:
1858:
1851:
1850:
1848:
1846:(EC 2.7.11.9)
1845:
1841:
1835:
1832:
1830:
1827:
1826:
1824:
1822:(EC 2.7.11.8)
1821:
1817:
1809:
1806:
1804:
1801:
1799:
1796:
1795:
1794:
1793:Aurora kinase
1791:
1790:
1788:
1786:(EC 2.7.11.7)
1785:
1781:
1775:
1772:
1771:
1769:
1767:(EC 2.7.11.6)
1766:
1762:
1756:
1753:
1751:
1748:
1746:
1743:
1741:
1738:
1737:
1735:
1733:(EC 2.7.11.5)
1732:
1728:
1722:
1719:
1717:
1714:
1712:
1709:
1708:
1706:
1704:(EC 2.7.11.4)
1703:
1699:
1691:
1688:
1686:
1683:
1681:
1678:
1677:
1675:
1671:
1668:
1666:
1663:
1662:
1660:
1656:
1653:
1651:
1648:
1647:
1645:
1642:
1641:
1639:
1637:(EC 2.7.11.3)
1636:
1632:
1626:
1623:
1621:
1618:
1616:
1613:
1611:
1608:
1607:
1605:
1603:(EC 2.7.11.2)
1602:
1598:
1590:
1587:
1586:
1585:
1582:
1578:
1575:
1573:
1570:
1568:
1565:
1563:
1560:
1559:
1558:
1557:EIF-2 kinases
1555:
1553:
1550:
1548:
1545:
1541:
1538:
1536:
1533:
1531:
1528:
1527:
1526:
1523:
1521:
1518:
1516:
1513:
1511:
1508:
1506:
1503:
1501:
1498:
1496:
1493:
1491:
1488:
1486:
1483:
1481:
1478:
1476:
1473:
1471:
1468:
1467:
1465:
1463:(EC 2.7.11.1)
1462:
1458:
1454:
1449:
1444:
1440:
1435:
1431:
1427:
1420:
1415:
1413:
1408:
1406:
1401:
1400:
1397:
1386:
1382:
1377:
1372:
1368:
1364:
1360:
1356:
1352:
1344:
1341:
1336:
1332:
1328:
1324:
1320:
1316:
1308:
1305:
1300:
1296:
1291:
1286:
1282:
1278:
1274:
1270:
1266:
1259:
1256:
1250:
1248:
1244:
1239:
1235:
1230:
1225:
1221:
1217:
1213:
1209:
1205:
1198:
1196:
1192:
1186:
1183:
1178:
1174:
1170:
1166:
1162:
1158:
1150:
1147:
1142:
1138:
1133:
1128:
1124:
1120:
1116:
1112:
1108:
1100:
1097:
1092:
1088:
1083:
1078:
1074:
1070:
1066:
1062:
1058:
1051:
1049:
1045:
1040:
1036:
1031:
1026:
1022:
1018:
1014:
1007:
1004:
999:
995:
990:
985:
981:
977:
973:
969:
965:
958:
955:
950:
946:
941:
936:
932:
928:
924:
917:
914:
909:
905:
900:
895:
891:
887:
883:
879:
875:
867:
865:
861:
855:
853:
851:
849:
847:
843:
838:
834:
829:
824:
820:
816:
812:
808:
804:
796:
793:
788:
784:
779:
774:
770:
766:
762:
755:
752:
747:
743:
739:
735:
731:
727:
723:
719:
715:
711:
704:
701:
696:
692:
688:
684:
680:
676:
672:
668:
660:
657:
652:
648:
643:
638:
634:
630:
626:
619:
616:
611:
607:
602:
597:
592:
587:
583:
579:
575:
571:
567:
560:
557:
552:
548:
543:
538:
534:
530:
526:
522:
518:
511:
508:
503:
499:
494:
489:
485:
481:
480:J. Biol. Chem
477:
470:
467:
462:
458:
453:
448:
444:
440:
436:
432:
428:
421:
418:
413:
409:
404:
399:
395:
391:
387:
380:
378:
376:
374:
372:
370:
366:
361:
357:
353:
349:
344:
339:
335:
331:
327:
320:
318:
314:
309:
305:
301:
297:
293:
289:
282:
279:
273:
271:
267:
263:
259:
254:
251:
244:
242:
238:
231:
229:
225:
218:
216:
209:
207:
203:
199:
195:
191:
187:
180:
178:
174:
166:
159:
154:
152:
144:
143:
142:
135:
130:
128:
124:
122:
117:
110:
104:
101:
97:
93:
92:
91:
88:
86:
82:
78:
74:
69:
66:
62:
58:
54:
50:
46:
42:
38:
34:
30:
19:
4588:Lestaurtinib
4579:
4549:
4487:Ritlecitinib
4419:Lestaurtinib
4366:Upadacitinib
4195:Fontolizumab
4186:
4171:
4150:
4139:Rontalizumab
4120:
3978:
3933:Pegacaristim
3924:
3883:
3853:
3846:M-CSF (CSF1)
3826:Mavrilimumab
3822:
3816:Sargramostim
3806:Molgramostim
3791:Ecogramostim
3787:
3760:Nartograstim
3731:
3724:G-CSF (CSF3)
3709:Peginesatide
3689:Epoetin zeta
3654:Epoetin beta
3649:Epoetin alfa
3620:
3525:Translocases
3522:
3509:
3496:
3483:
3470:
3460:Transferases
3457:
3444:
3301:Binding site
2732:P70S6 kinase
1358:
1354:
1343:
1318:
1314:
1307:
1272:
1268:
1258:
1211:
1207:
1185:
1160:
1156:
1149:
1114:
1110:
1099:
1064:
1060:
1020:
1016:
1006:
971:
967:
957:
930:
926:
916:
881:
877:
810:
806:
795:
768:
764:
754:
713:
709:
703:
670:
666:
659:
632:
628:
618:
573:
569:
559:
524:
520:
510:
483:
479:
469:
434:
430:
420:
393:
389:
333:
329:
291:
287:
281:
253:
239:
235:
226:
222:
213:
204:
200:
196:
192:
188:
184:
175:
171:
149:
139:
125:
120:
118:
114:
89:
70:
63:(NF-κB) and
43:(PAMPs) and
32:
28:
26:
4598:Quizartinib
4593:Midostaurin
4482:Peficitinib
4444:Ruxolitinib
4439:Peficitinib
4394:Baricitinib
4356:Ruxolitinib
4351:Peficitinib
4346:Oclacitinib
4341:Momelotinib
4326:Baricitinib
4321:Abrocitinib
4229:Interleukin
4187:Antibodies:
4144:Sifalimumab
4129:Faralimomab
4124:Anifrolumab
4121:Antibodies:
3943:Romiplostim
3928:Eltrombopag
3897:SCF (c-Kit)
3823:Antibodies:
3811:Regramostim
3745:Lenograstim
3296:Active site
3183:(EC 2.7.12)
2570:Polo kinase
2510:Polo kinase
4660:Immunology
4649:Categories
4583:Emfilermin
4434:Pacritinib
4336:Filgotinib
4302:inhibitors
4190:Emapalumab
3962:Interferon
3887:Agerafenib
3877:Mirimostim
3867:Lanimostim
3801:Milodistim
3750:Leridistim
3735:Filgrastim
3576:modulators
3499:Isomerases
3473:Hydrolases
3340:Regulation
1861:IκB kinase
1436:2.7.11-12)
1067:(1): 1–7.
294:(1): 3–9.
245:References
121:Drosophila
57:IκB kinase
4655:EC 2.7.11
4608:Sunitinib
4603:Sorafenib
4512:ZM-449829
4502:WHI-P 154
4492:TCS-21311
4429:NSC-33994
4384:Atiprimod
4172:Agonists:
4154:Bifarcept
3979:Agonists:
3925:Agonists:
3857:Cilmostim
3854:Agonists:
3831:Namilumab
3788:Agonists:
3732:Agonists:
3621:Agonists:
3584:Chemokine
3378:EC number
1987:PKC alpha
131:Structure
111:Discovery
95:survival.
4507:ZM-39923
4424:NSC-7908
4389:AZD-1480
4280:instead.
4260:instead.
4240:instead.
4216:instead.
4134:MEDI-545
3908:instead.
3836:Otilimab
3639:CNTO-530
3595:instead.
3402:Kinetics
3326:Cofactor
3289:Activity
2343:KIAA0999
2238:MAPKAPK5
2233:MAPKAPK3
2228:MAPKAPK2
1385:17503328
1335:19181383
1299:23531543
1238:25290089
1177:25728511
1141:16286015
1111:Immunity
1091:18249132
1061:Cytokine
1039:15465816
998:18824541
949:15695821
908:15767370
765:Immunity
746:42977425
695:25609420
651:15292196
610:11960013
502:12034707
461:19689377
412:12620219
360:29267200
352:17667936
308:14751757
4639:Biology
4449:SD-1008
3624:ARA-290
3512:Ligases
3282:Enzymes
3002:MAP3K14
2980:MAP3K11
2975:MAP3K10
2965:MAP3K13
2960:MAP3K12
2762:RPS6KC1
2757:RPS6KA1
2752:RPS6KA3
2747:RPS6KA2
2742:RPS6KB2
2727:RPS6KA4
2722:RPS6KA5
2373:Kalirin
2338:SNF1LK2
1577:EIF2AK4
1572:EIF2AK3
1426:Kinases
1376:1867098
1290:3686650
1229:4453441
1132:7111074
1082:2377356
989:2593423
899:2213113
837:9625767
828:2212370
787:9430229
738:8599092
718:Bibcode
710:Science
687:8026518
578:Bibcode
551:9151903
542:2196288
452:3182414
4625:Portal
4543:Others
4409:CYT387
4399:CHZ868
4288:Others
4044:IFNA21
4040:IFNA17
4036:IFNA16
4032:IFNA14
4028:IFNA13
4024:IFNA10
3486:Lyases
3232:MAP2K7
3227:MAP2K6
3222:MAP2K5
3217:MAP2K4
3212:MAP2K3
3207:MAP2K2
3202:MAP2K1
3153:ACVRL1
3148:ACVR2B
3143:ACVR2A
3138:ACVR1C
3133:ACVR1B
3116:BMPR1B
3111:BMPR1A
2985:MAP3K7
2970:MAP3K9
2921:MAP3K8
2916:MAP3K7
2911:MAP3K6
2906:MAP3K5
2901:MAP3K4
2896:MAP3K3
2891:MAP3K2
2886:MAP3K1
2860:MAPK14
2855:MAPK13
2850:MAPK11
2838:MAPK10
2816:MAPK15
2811:MAPK12
2703:CDC2L1
2678:CDC2L5
2353:SNF1LK
2178:CAMK2G
2173:CAMK2D
2168:CAMK2B
2163:CAMK2A
2153:CAMK1G
2148:CAMK1D
2143:CAMK1B
2138:CAMK1A
1992:PRKCB1
1929:PRKACA
1924:PRKACB
1919:PRKACG
1895:IKBKAP
1721:BCKDHB
1716:BCKDHA
1690:PRKAG3
1685:PRKAG2
1680:PRKAG1
1670:PRKAB2
1665:PRKAB1
1655:PRKAA2
1650:PRKAA1
1495:STK38L
1383:
1373:
1333:
1297:
1287:
1236:
1226:
1175:
1139:
1129:
1089:
1079:
1037:
996:
986:
947:
906:
896:
835:
825:
785:
744:
736:
693:
685:
649:
608:
601:122810
598:
549:
539:
500:
459:
449:
410:
358:
350:
306:
264:(MeSH)
219:Cancer
83:, and
4083:IFNB3
4079:IFNB1
4020:IFNA8
4016:IFNA7
4012:IFNA6
4008:IFNA5
4004:IFNA4
4000:IFNA2
3996:IFNA1
3438:Types
3194:MAP2K
3128:ACVR1
3121:BMPR2
3106:BMPR1
3031:GSK-3
2872:MAP3K
2833:MAPK9
2828:MAPK8
2806:MAPK7
2801:MAPK6
2796:MAPK4
2791:MAPK3
2786:MAPK1
2698:PFTK1
2693:PCTK3
2688:PCTK2
2683:PCTK1
2673:CDK12
2668:CDK10
2643:CDKL5
2623:CDKL2
2500:STK19
2495:EEF2K
2476:PHKG2
2471:PHKG1
2461:PHKA2
2456:PHKA1
2437:MYLK4
2432:MYLK3
2427:MYLK2
2403:DCLK1
2398:Titin
2388:TRIB3
2383:TRIB2
2378:TRIB1
2368:TSSK2
2348:STK40
2333:PSKH1
2328:PRKD3
2323:PRKD2
2303:PHKG2
2298:PHKG1
2288:OBSCN
2283:NUAK2
2278:NUAK1
2273:MKNK2
2268:MKNK1
2258:MARK4
2253:MARK3
2248:MARK2
2243:MARK1
2223:STK11
2218:DAPK3
2213:DAPK2
2208:DAPK1
2203:CHEK2
2198:CHEK1
2183:CAMK4
2158:CAMK2
2133:CAMK1
2128:BRSK2
2022:PRKCQ
2017:PRKCI
2012:PRKCG
2007:PRKCH
2002:PRKCE
1997:PRKCD
1958:PRKG1
1890:IKBKG
1885:IKBKE
1834:STK10
1829:FASTK
1755:IDH3G
1750:IDH3B
1745:IDH3A
1711:BCKDK
1505:ROCK1
1490:STK38
1485:MAST2
1480:MAST1
1475:LATS2
1470:LATS1
742:S2CID
691:S2CID
356:S2CID
85:IRAK4
81:IRAKM
77:IRAK2
73:IRAK1
49:MyD88
4522:TYK2
4464:JAK3
4376:JAK2
4313:JAK1
4278:here
4276:See
4258:here
4256:See
4249:TGFβ
4238:here
4236:See
4214:here
3906:here
3904:See
3593:here
3591:See
3530:list
3523:EC7
3517:list
3510:EC6
3504:list
3497:EC5
3491:list
3484:EC4
3478:list
3471:EC3
3465:list
3458:EC2
3452:list
3445:EC1
3021:TPK1
2997:CDC7
2955:MLKs
2948:KSR2
2943:KSR1
2938:BRAF
2933:ARAF
2928:RAFs
2663:CDK9
2658:CDK8
2653:CDK7
2648:CDK6
2638:CDK5
2633:CDK4
2628:CDK3
2618:CDK2
2613:CDK1
2594:PLK4
2589:PLK3
2584:PLK2
2579:PLK1
2534:PLK4
2529:PLK3
2524:PLK2
2519:PLK1
2466:PHKB
2422:MYLK
2393:TRIO
2363:SPEG
2358:SNRK
2318:PKD1
2313:PIM2
2308:PIM1
2293:PASK
2263:MELK
2193:CASK
2188:MLCK
2109:GRK6
2104:GRK5
2099:GRK4
2037:PKN3
2032:PKN2
1934:PRKY
1880:TBK1
1875:IKK2
1870:CHUK
1774:STK4
1740:IDH2
1625:PDK4
1620:PDK3
1615:PDK2
1610:PDK1
1589:WEE1
1584:Wee1
1552:mTOR
1540:AKT3
1535:AKT2
1530:AKT1
1520:SGK3
1515:SGK2
1381:PMID
1331:PMID
1295:PMID
1234:PMID
1173:PMID
1137:PMID
1087:PMID
1035:PMID
994:PMID
945:PMID
904:PMID
833:PMID
783:PMID
734:PMID
683:PMID
647:PMID
606:PMID
547:PMID
498:PMID
457:PMID
408:PMID
348:PMID
304:PMID
146:one.
99:LPS.
33:IRAK
27:The
4296:JAK
4269:TNF
3604:CSF
3026:TTK
2990:ZAK
1567:HRI
1562:PKR
1510:SGK
1500:CIT
1371:PMC
1363:doi
1323:doi
1285:PMC
1277:doi
1273:138
1224:PMC
1216:doi
1212:112
1165:doi
1127:PMC
1119:doi
1077:PMC
1069:doi
1025:doi
1021:279
984:PMC
976:doi
935:doi
931:280
894:PMC
886:doi
882:201
823:PMC
815:doi
811:187
773:doi
726:doi
714:271
675:doi
637:doi
633:279
596:PMC
586:doi
537:PMC
529:doi
525:185
488:doi
484:277
447:PMC
439:doi
398:doi
338:doi
296:doi
4651::
4081:,
4042:,
4038:,
4034:,
4030:,
4026:,
4022:,
4018:,
4014:,
4010:,
4006:,
4002:,
3998:,
1676:γ
1661:β
1646:α
1434:EC
1428::
1379:.
1369:.
1359:80
1357:.
1353:.
1329:.
1319:46
1317:.
1293:.
1283:.
1271:.
1267:.
1246:^
1232:.
1222:.
1210:.
1206:.
1194:^
1171:.
1161:27
1159:.
1135:.
1125:.
1115:23
1113:.
1109:.
1085:.
1075:.
1065:42
1063:.
1059:.
1047:^
1033:.
1019:.
1015:.
992:.
982:.
972:28
970:.
966:.
943:.
929:.
925:.
902:.
892:.
880:.
876:.
863:^
845:^
831:.
821:.
809:.
805:.
781:.
767:.
763:.
740:.
732:.
724:.
712:.
689:.
681:.
671:24
669:.
645:.
631:.
627:.
604:.
594:.
584:.
574:99
572:.
568:.
545:.
535:.
523:.
519:.
496:.
482:.
478:.
455:.
445:.
433:.
429:.
406:.
394:11
392:.
388:.
368:^
354:.
346:.
334:85
332:.
328:.
316:^
302:.
292:16
290:.
269:^
79:,
75:,
4627::
4304:)
4300:(
4085:)
4077:(
4046:)
3994:(
3565:e
3558:t
3551:v
3532:)
3528:(
3519:)
3515:(
3506:)
3502:(
3493:)
3489:(
3480:)
3476:(
3467:)
3463:(
3454:)
3450:(
3274:e
3267:t
3260:v
3083:-
3066:-
3049:-
1852:-
1432:(
1418:e
1411:t
1404:v
1387:.
1365::
1337:.
1325::
1301:.
1279::
1240:.
1218::
1179:.
1167::
1143:.
1121::
1093:.
1071::
1041:.
1027::
1000:.
978::
951:.
937::
910:.
888::
839:.
817::
789:.
775::
769:7
748:.
728::
720::
697:.
677::
653:.
639::
612:.
588::
580::
553:.
531::
504:.
490::
463:.
441::
435:9
414:.
400::
362:.
340::
310:.
298::
31:(
20:)
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