Integrins are a large family of heterodimeric transmembrane glycoproteins that attach cells to extracellular matrix proteins of the basement membrane or to ligands on other cells. Integrins contain large (α) and small (β) subunits of sizes 120-170 kDa and 90-100 kDa, respectively. Some integrins mediate direct cell to cell recognition and interactions. Integrins contain binding sites for divalent cations Mg2+ and Ca2+, which are necessary for their adhesive function. Mammalian integrins form several subfamilies sharing common β subunits that associate with different α subunits.

β2 integrins are exclusively expressed on leukocytes and undergo a conformational change encompassing the phosphorylation of the β subunit upon activation. However, this phosphorylation is neither necessary nor sufficient for conformational activation. Theactivation status is controlled by the GFFKR site immediately adjacent to the transmembrane domain of the alpha chain. A structural model of a β2 integrin (Harris et al. 2000) is suggested by site-directed mutagenesis and truncation mutants (link to Harris, E.S., McIntyre, T.M., Prescott, S.M., and Zimmerman, G.A. The leukocyte integrins. J.Biol.Chem. 275(31):23409-23412, 2000) β2 integrins include 4 different heterodimers CD11a/CD18 [Lymphocyte Function-Associated Antigen-1] (LFA-1) the predominant β2 integrin, CD11b/CD18 (Mac-1) exclusive to granulocytes and monocytes, CD11c/CD18 (p150,95), and CD11d/CD18. A mutation in the gene encoding the β2 (CD18) molecule results in a genetic disorder, LAD, Leukocyte Adhesion Deficiency. LAD patients have recurrent bacterial infections due to the inability to effectively recruit granulocytes in response to infections.

The most important member of the β1 integrin subfamily on leukocytes is Very Late Antigen-4 (VLA-4, CD49d/CD29, α4 β1). VLA-4 binds to its ligand VCAM-1, and is chiefly responsible for lymphocyte adhesion to vascular endothelium and leukocyte recruitment to the inflamed area.


LFA-1 | Mac-1 | VLA-4 | p150,95

Click here for a graphical Structure of Integrins and diagrams concerning integrin activation.

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