Cross talk among TGF-ß signaling pathways, integrins, and the extracellular matrix.

ABSTRACT

The growth factor TGF-ß is secreted in a latent complex consisting of three proteins TGF-ß, an inhibitor (latency-associated protein, LAP, which is derived from the TGF-ß propeptide) and an ECM-binding protein (one of the latent TGF-ß binding proteins, or LTBPs). LTBPs interact with fibrillins and other ECM components and thus function to localize latent TGF-ß in the ECM. LAP contains an integrin-binding site (RGD), and several RGD-binding integrins are able to activate latent TGF-ß through binding this site. Mutant mice defective in integrin-mediated activators, and humans and mice with fibrillin gene mutations, show the critical role of ECM and integrins in regulating TGF-ß signaling.