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, p62dok, 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 p62dok, which then binds rasGAP. A monoclonal antibody, 2C4, to the rasGAP-associated p62 reacts with p62dok. Thus, p62dok appears to be the long-sought major substrate of many tyrosine kinases.
Yamanashi
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Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Baltimore
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D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites; D015152:Blotting, Northern; D002460:Cell Line; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000276:immunology; D020690:GTPase-Activating Proteins; D051379:Mice; D008969:Molecular Sequence Data; D016374:Oncogene Proteins v-abl / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D018909:src Homology Domains
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C489561:Dok1 protein, mouse; C074561:GAP-associated protein p62; D020690:GTPase-Activating Proteins; D016374:Oncogene Proteins v-abl; D010750:Phosphoproteins; D011506:Proteins; D016601:RNA-Binding Proteins; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases