92:, an intracellular g-protein. Rap1 assists in breaking the constraint between the alpha and beta subunits of LFA-1. This induces an intermediate extended conformation. The conformational change stimulates a recruitment of proteins to form an activation complex. The activation complex further destabilizes the alpha and beta subunits. Chemokines also stimulate an I-like domain on the beta subunit, which causes the MIDAS site on the beta subunit to bind to glutamate on the I domain of the alpha subunit. This binding process causes the beta subunit to pull down the alpha 7 helix of the I domain, exposing and opening up the MIDAS site on the alpha subunit for binding. This causes LFA-1 to undergo a conformational change to the fully extended conformation. The process of activating LFA-1 is known as inside out signaling, which causes LFA-1 to shift from low affinity to high affinity by opening the ligand-binding site.
117:, a subtype of LAD, is caused by a lack of integrins that contain the beta subunit, including LFA-1. LAD1 is characterized by recurring bacterial infection, delayed (>30 days) separation of umbilical cord, ineffective wound healing and pus formation, and granulocytosis. LAD1 is caused by low expression of CD11 and CD18. CD18 is found on chromosome 21 and CD11 is found on chromosome 16.
100:
Early discovery of cellular adhesion molecules involved the use of monoclonal antibodies to inhibit cellular adhesion processes. The antigen that bound to the monoclonal antibodies was identified as an important molecule in cellular recognition processes. These experiments yielded the protein name
112:
is an immunodeficiency caused by the absence of key adhesion surface proteins, including LFA-1. LAD is a genetic defect caused by autosomal recessive genes. The deficiency causes ineffective migration and phagocytosis for impacted leukocytes. Patients with LAD also have poorly functioning
76:. The ICAM binding site is on the alpha subunit. The general binding region of the alpha subunit is the I-domain. Due to the presence of a divalent cation site in the I-domain, the specific binding site is often referred to as the metal-ion dependent adhesion site (MIDAS).
101:“integrin” as a description of the proteins' integral role in cellular adhesion processes and the transmembrane association between the extracellular matrix and the cytoskeleton. LFA-1, a leukocyte integrin, was first discovered by Timothy Springer in mice in the 1980s.
42:
and other leukocytes. LFA-1 plays a key role in emigration, which is the process by which leukocytes leave the bloodstream to enter the tissues. LFA-1 also mediates firm arrest of leukocytes. Additionally, LFA-1 is involved in the process of
67:
LFA-1 is a heterodimeric glycoprotein with non-covalently linked subunits. LFA-1 has two subunits designated as the alpha subunit and beta subunit. The alpha subunit was named aL in 1983. The alpha subunit is designated
55:, ICAM-3, ICAM-4, ICAM-5, and JAM-A. LFA-1/ICAM-1 interactions have recently been shown to stimulate signaling pathways that influence T cell differentiation. LFA-1 belongs to the
617:
586:
1563:
475:"Lymphocyte function-associated antigen 1 (LFA-1): a surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing"
610:
84:
In an inactive state, LFA-1 rests in a bent conformation and has a low affinity for ICAM binding. This bent conformation conceals the MIDAS.
1168:
427:
Anderson DC, Springer TA (1987). "Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins".
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mediated killing as well as antibody mediated killing by granulocytes and monocytes. As of 2007, LFA-1 has 6 known ligands:
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528:"Secondary T cell-T cell synaptic interactions drive the differentiation of protective CD8+ T cells"
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stimulate the activation process of LFA-1. The activation process begins with the activation of
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GĂ©rard A, Khan O, Beemiller P, Oswald E, Hu J, Matloubian M, Krummel MF (April 2013).
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Janeway, Travers, Walport, Shlomchik, Immunobiology 6th ed. (2005) Garland
Science:NY
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Parham, Peter, The Immune System 3rd ed. (2009) Garland
Science: London and New York
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Proceedings of the
National Academy of Sciences of the United States of America
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294:"Not Just an Adhesion Molecule: LFA-1 Contact Tunes the T Lymphocyte Program"
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Davignon D, Martz E, Reynolds T, KĂĽrzinger K, Springer TA (July 1981).
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Akbari H, Zadeh MM (January 2001). "Leukocyte adhesion deficiency".
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72:; and the beta subunit, unique to leukocytes, is beta-2 or
261:
Oxford dictionary of biochemistry and molecular biology
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263:(Rev. ed.). Oxford: Oxford University Press.
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219:Adhesion molecules : function and inhibition
159:(1st ed.). Oxford: Oxford University Press.
134:, a drug that blocks LFA-1 from binding to ICAM-1
348:Protein-protein interactions in drug discovery
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579:at the U.S. National Library of Medicine
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28:Lymphocyte function-associated antigen 1
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292:Verma NK, Kelleher D (August 2017).
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441:10.1146/annurev.me.38.020187.001135
105:Leukocyte Adhesion Deficiency (LAD)
59:superfamily of adhesion molecules.
1564:cell surface receptor deficiencies
25:
1:
127:Leukocyte adhesion deficiency
110:Leukocyte adhesion deficiency
1424:Leukocyte-adhesion receptor:
386:Indian Journal of Pediatrics
1483:Very late antigen receptor:
157:A dictionary of biomedicine
1605:
1084:Lymphocyte homing receptor
1559:
429:Annual Review of Medicine
1116:Carcinoembryonic antigen
970:Unconventional/ungrouped
581:Medical Subject Headings
311:10.4049/jimmunol.1700495
631:cell adhesion molecules
589:Info with links in the
350:. Weinheim: Wiley-VCH.
591:Cell Migration Gateway
500:10.1073/pnas.78.7.4535
1535:Vitronectin receptor:
1398:Fibronectin receptor:
1351:Glycoprotein IIb/IIIa
1339:Cytoadhesin receptor:
823:Glycoprotein IIb/IIIa
298:Journal of Immunology
223:. Basel: Birkhauser.
1526:Integrin alpha6beta1
1500:Integrin alpha3beta1
1495:Integrin alpha2beta1
1490:Integrin alpha1beta1
1463:Integrin alphaXbeta2
1447:Macrophage-1 antigen
1415:Integrin alpha5beta1
1410:Integrin alpha4beta1
1405:Integrin alpha2beta1
1378:Macrophage-1 antigen
1371:Fibrinogen receptor:
1346:Integrin alpha6beta4
795:Macrophage-1 antigen
781:Integrin alphaXbeta2
660:Myelin protein zero
639:Calcium-independent
491:1981PNAS...78.4535D
398:10.1007/bf02728867
346:Dömling A (2013).
259:Cammack R (2006).
155:Lackie JM (2010).
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846:Calcium-dependent
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627:Membrane proteins
532:Nature Immunology
16:(Redirected from
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113:neutrophils.
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920:Desmocollin
587:ITGAL ITGB2
392:(1): 77–9.
132:Lifitegrast
40:lymphocytes
1584:Immunology
1578:Categories
1093:L-selectin
1064:P-selectin
1059:L-selectin
1054:E-selectin
977:T-cadherin
898:Desmoglein
890:Desmosomal
435:: 175–94.
139:References
86:Chemokines
80:Activation
1589:Integrins
1562:see also
1178:Integrins
1046:Selectins
863:Classical
855:Cadherins
759:Integrins
690:L1 family
366:828743731
279:743217704
239:261225084
175:663104793
96:Discovery
63:Structure
38:found on
1099:integrin
648:IgSF CAM
562:23475183
414:11336052
406:11237241
320:28784685
121:See also
57:integrin
36:integrin
34:) is an
553:3962671
519:7027264
487:Bibcode
449:3555290
1356:ITGA2B
1332:Dimers
961:PCDH19
956:PCDH15
827:ITGA2B
717:Nectin
695:L1-CAM
685:PE-CAM
680:VCAM-1
583:(MeSH)
560:
550:
517:
510:319826
507:
447:
412:
404:
364:
354:
318:
277:
267:
237:
227:
173:
163:
53:ICAM-2
49:ICAM-1
1510:CD49d
1505:VLA-4
1468:CD11c
1452:CD11b
1436:CD11a
1431:LFA-1
1383:CD11b
1360:ITGB3
1185:Alpha
1136:EpCAM
1131:CD146
1108:LFA-1
1104:VLA-4
1077:Other
1032:CDH10
1022:CDH17
1017:CDH16
1012:CDH15
1007:CDH12
1002:CDH11
951:PCDH1
831:ITGB3
813:CD49d
809:VLA-4
799:CD11b
785:CD11c
771:CD11a
767:LFA-1
747:CD155
742:CADM3
737:CADM1
732:PVRL3
727:PVRL2
722:PVRL1
705:NFASC
700:NRCAM
656:N-CAM
577:LFA-1
410:S2CID
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1387:CD18
1281:Beta
1126:CD44
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558:PMID
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362:OCLC
352:ISBN
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225:ISBN
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