Anti-LRRC32 Anticorps [GARP5] (A86349)

Glycoprotein-A repetitions predominant protein (GARP) associates with latent transforming growth factor-ß (proTGFß) on the surface of T regulatory cells and platelets; however, whether GARP functions in latent TGFß activation and the structural basis of coassociation remain unknown. We find that Cys-192 and Cys-331 of GARP disulfide link to the TGFß1 prodomain and that GARP with C192A and C331A mutations can also noncovalently associate with proTGFß1. Noncovalent association is sufficiently strong for GARP to outcompete latent TGFß-binding protein for binding to proTGFß1. Association between GARP and proTGFß1 prevents the secretion of TGFß1. Integrin a(V)ß(6) and to a lesser extent a(V)ß(8) are able to activate TGFß from the GARP-proTGFß1 complex. Activation requires the RGD motif of latent TGFß, disulfide linkage between GARP and latent TGFß, and membrane association of GARP. Our results show that GARP is a latent TGFß-binding protein that functions in regulating the bioavailability and activation of TGFß.