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Related Pathways Integrin Signaling Caveolar-mediated Endocytosis View All Pathways

Synonyms: ALPHA1 INTEGRIN, CD49A, E130012M19RIK, INTEGRIN ALPHA 1, ITGA1, VLA1

Integrin Pathway

Integrins along with the immunoglobulin superfamily, selectins, cadherins and mucins comprise the five major groups of cell adhesion molecules. Integrins are cell-surface transmembrane heterodimeric (α/β) glycoproteins that mediate external cell-cell and cell-matrix (substratum) interactions and internal linkage to the cytoskeleton and cell signaling pathways. Integrins mediate signaling from the extracellular space into the cell via adaptor molecules such as focal adhesion kinase (FAK), integrin-linked kinase (ILK), particularly interesting new cysteine-histidine rich protein (PINCH) and non-catalytic (region of) tyrosine kinase adaptor protein 2 (Nck2). Activated pathways signal a variety of processes including survival/apoptosis, proliferation, cell-cycle progression, cell shape, polarity, adhesion, migration and differentiation.

The integrin family includes least 24 heterodimers assembled from 18 alpha and 8 beta subunits. Integrin heterodimers contain binding sites for divalent magnesium and calcium that facilitate their binding of ligands. Integrins differentially bind to extracellular matrix proteins such as collagen, elastin, laminin, fibronectin and vitronectin and cell associated ligands such as ICAMs and VCAMs. Integrin ligands also include CCN1, cysteine rich protein 61 (CCN1), developmental locus-1 (Del-1); tenascin-c (TNC), thrombospondin (TSP), osteopontin (OPN), von Willebrand factor (vWF), matrix metalloproteinase (MMP) and bone sialo protein (BSP).

The integrin family has eight subfamilies designated as beta 1 through beta 8. The integrins have also been grouped by function into the RGD, I-domain, and laminin binding, alpha 4 and the leukocyte subfamilies. The most widely studied subfamilies are beta 1 (CD29, very late activation (VLA) members); beta 2 (leukocyte integrins such as CD11a/CD18, Lymphocyte Function-Associated Antigen-1, (LFA-1)); CD11b/CD18 (Mac-1); CD11c/CD18; alpha d beta 2; beta 3 (CD61, cytoadhesions), and beta 7 (alpha 4 beta 7 and alpha E beta 7).