DIRECT ASSOCIATION OF PROTEIN-TYROSINE-PHOSPHATASE PTP-PEST WITH PAXILLIN

Tyrosine phosphorylation of focal adhesion-associated proteins may be involved in the regulation of the cytoskeleton and in the control of s ignals for growth and survival, The focal adhesion kinase (FAK) functi ons in regulating tyrosine phosphorylation of several of these protein s, including paxillin, tensin, and p130(cas). Proetin-tyrosine phospha tases, the counterparts of protein-tyrosine kinases, also presumably r egulate phosphorylation of these proteins, We have tested the hypothes is that FAK intimately associates with a protein-tyrosine phosphatase, Protein-tyrosine phosphatase activity associated with the recombinant C-terminal domain of FAK in vitro and could be coimmunoprecipitated w ith both FAK and paxillin from lysates of chicken embryo cells, Howeve r, the interaction with FAK appeared to be indirect and mediated via p axillin, The protein-tyrosine phosphatase was subsequently identified as protein tyrosine phosphatase-PEST, a nonreceptor protein-tyrosine p hosphatase. The C-terminal noncatalytic domain of protein-tyrosine pho sphatase-PEST directly bound to paxillin in vitro, The association of both a protein-tyrosine kinase and a protein-tyrosine phosphatase with paxillin suggests that paxillin may play a critical role in the regul ation of the phosphotyrosine content of proteins in focal adhesions.