Integrin alpha-6/beta-1 is a receptor for laminin on platelets. Integrin alpha-6/beta-4 is a receptor for laminin in epithelial cells and it plays a critical structural role in the hemidesmosome (By similarity). ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760).
Integrin alpha-6/beta-4 is predominantly expressed by epithelia. Isoforms containing segment X1 are ubiquitously expressed. Isoforms containing segment X1X2 are expressed in heart, kidney, placenta, colon, duodenum, myoblasts and myotubes, and in a limited number of cell lines; they are always coexpressed with the ubiquitous isoform containing segment X1. In some tissues (e.g. Salivary gland), isoforms containing cytoplasmic segment A and isoforms containing segment B are detected while in others, only isoforms containing one cytoplasmic segment are found (segment A in epidermis and segment B in kidney).
Involvement in disease
Epidermolysis bullosa letalis, with pyloric atresia
Belongs to the integrin alpha chain family. Contains 7 FG-GAP repeats.
Isoforms containing segment A, but not segment B, are the major targets for PMA-induced phosphorylation. Phosphorylation occurs on 'Ser-1103' of isoform alpha-6X1X2A. Phosphorylation is not required for the induction of integrin alpha-6A/beta-1 high affinity but may reduce the affinity for ligand. In invasive prostate cancer ITGA6 undergoes PLAU-mediated cleavage at residues Arg-634-635-Arg in a time-dependent manner enhancing cell invasion and migration in vitro. Palmitoylation by DHHC3 enhances stability and cell surface expression.
Iglesia RP et al. Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells. Stem Cell Res Ther8:76 (2017).
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Zhao F et al. Up-regulation of integrin a6ß4 expression by mitogens involved in dairy cow mammary development. In Vitro Cell Dev Biol Anim51:287-99 (2015).
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