SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility

The transmembrane glycoprotein SHPS-1 binds the protein tyrosine phosphatas e SHP-2 and serves as its substrate. Although SHPS-1 has been implicated in growth factor- and cell adhesion-induced signaling, its biological role ha s remained unknown. Fibroblasts homozygous for expression of an SHPS-1 muta nt lacking most of the cytoplasmic region of this protein exhibited increas ed formation of actin stress fibers and focal adhesions. They spread more q uickly on fibronectin than did wild-type cells, but they were defective in subsequent polarized extension and migration. The extent of adhesion-induce d activation of Rho, but not that of Rac, was also markedly reduced in the mutant cells. Activation of the Ras-extracellular signal-regulated kinase s ignaling pathway and of c-Jun N-terminal kinases by growth factors was eith er unaffected or enhanced in the mutant fibroblasts. These results demonstr ate that SHPS-1 plays crucial roles in integrin-mediated cytoskeletal reorg anization, cell motility and the regulation of Rho, and that it also negati vely modulates growth factor-induced activation of mitogen-activated protei n kinases.