Beta 1 integrin-mediated signaling in human T cells.

Beta 1 integrin/ligand binding evokes tyrosine phosphorylation of various proteins. In our previous studies, we have shown that the engagement of beta integrin molecules induced tyrosine phosphorylation of 140, 120, 110-105, 80-70, 60-55 and 45 KD proteins in peripheral T lymphocytes. Several tyrosine-phosphorylated proteins have been identified such as PLC gamma (pp140), pp125FAK(pp120), Paxillin(pp70), p59fyn/p56lck(pp60-55) and MAPkinase (pp45). However, a 105 KD tyrosine-phosphorylated protein(pp105) has not been identified. Recently, we demonstrated that pp105 is identified as a novel p130Cas related protein. pp105 is preferentially expressed in lymphoid cells, while p130Cas is expressed in adherent cells. With these findings, we designated pp105 as Cas-L, "lymphocyte type Cas." Cas-L is directly associated with FAk-C-terminal region in an integrin stimulation-dependent manner, and tyrosine phosphorylated Cas-L binds to the SH2 domains of Crk, Nck and SHPTP2. These findings reveal a novel architecture of beta 1 integrin-mediated protein tyrosine phosphorylation and further suggest the involvement of Crk, Nck and SHPTP2 in the downstream of beta 1 integrin-mediated signaling pathway.