STRUCTURE AND FUNCTION OF CAS-L, A 105-KD CRK-ASSOCIATED SUBSTRATE-RELATED PROTEIN THAT IS INVOLVED IN BETA-1 INTEGRIN-MEDIATED SIGNALING IN LYMPHOCYTES

Integrin/ligand binding evokes tyrosine phosphorylation of various pro teins. We reported previously that a 105 kD protein (pp105) was tyrosi ne phosphorylated by the engagement of beta 1 integrins in T lymphocyt es. We show here that pp105 is a novel p130Cas (Crk-associated substra te)-related protein. Deduced amino acid sequence revealed that pp105 c ontains conserved motifs with p130Cas, and both pp105 and p130Cas bind to focal adhesion kinase (pp125FAK) and Crk. However, pp105 has a cle arly distinct structure from p130Cas, and pp105 is preferentially expr essed in lymphocytes, whereas p130Cas is expressed in adherent cells. With these findings, we designate pp105 as Cas-L, lymphocyte-type Cas. Furthermore, we demonstrate that integrin/ligand binding results in t he recruitment of Crk, Nck, and SHPTP2 to pp105. These findings furthe r define the roles of pp105/Cas-L and pp125FAK in the integrin-mediate d signaling pathways.