Identification of the abl- and rasGAP-associated 62 kDa protein as a docking protein, dok

A 62 kDa protein is highly phosphorylated in many cells containing activated tyrosine kinases. This protein, characterized mainly by its avid association with rasGAP, has proved elusive. Anti-phosphotyrosine antibody was used to purify p62. From peptide sequence, molecular cloning revealed a cDNA encoding a novel protein, p62(dok), with little homology to others but with a prominent set of tyrosines and nearby sequences suggestive of SH2 binding sites. In cells, v-Abl tyrosine kinase binds and strongly phosphorylates p62(dok), which then binds rasGAP. A monoclonal antibody, 2C4, to the rasGAP-associated p62 reacts with p62(dok). Thus, p62(dok) appears to be the long-sought major substrate of many tyrosine kinases.