Identification of the Abl- and rasGAP-associated 62 kDa protein as a docking protein, Dok

Cell. 1997 Jan 24;88(2):205-11. doi: 10.1016/s0092-8674(00)81841-3.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Binding Sites
  • Blotting, Northern
  • Cell Line
  • Cell Line, Transformed
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / immunology
  • GTPase-Activating Proteins
  • Mice
  • Molecular Sequence Data
  • Oncogene Proteins v-abl / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / metabolism*
  • RNA-Binding Proteins / immunology
  • Sequence Homology, Amino Acid
  • Transfection
  • src Homology Domains

Substances

  • Antibodies, Monoclonal
  • DNA, Complementary
  • DNA-Binding Proteins
  • Dok1 protein, mouse
  • GAP-associated protein p62
  • GTPase-Activating Proteins
  • Oncogene Proteins v-abl
  • Phosphoproteins
  • Proteins
  • RNA-Binding Proteins
  • Phosphotyrosine
  • Protein-Tyrosine Kinases

Associated data

  • GENBANK/U78818