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

Y Yamanashi1, D Baltimore

  • 1Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.

Cell
|January 24, 1997
PubMed

Insights

Researchers identified p62dok, a novel protein highly phosphorylated by tyrosine kinases. This protein avidly associates with rasGAP, suggesting it is a major substrate for these kinases.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • A 62 kDa protein, associated with rasGAP, is highly phosphorylated by activated tyrosine kinases.
  • This key protein has remained elusive, hindering a full understanding of tyrosine kinase signaling pathways.

Purpose of the Study:

  • To identify and characterize the elusive 62 kDa protein phosphorylated by tyrosine kinases.
  • To elucidate the role of this protein in cellular signaling pathways involving rasGAP and tyrosine kinases.

Main Methods:

  • Purification of the 62 kDa protein using an anti-phosphotyrosine antibody.
  • Peptide sequencing and molecular cloning to identify the protein's cDNA.
  • Characterization of the novel protein, named p62dok, and its interactions with v-Abl tyrosine kinase and rasGAP.

Main Results:

  • A novel protein, p62dok, was identified with multiple tyrosine residues and potential SH2 binding sites.
  • p62dok is strongly phosphorylated by v-Abl tyrosine kinase and subsequently binds to rasGAP.
  • A monoclonal antibody (2C4) against the rasGAP-associated p62 protein also recognizes p62dok.

Conclusions:

  • p62dok is identified as the long-sought major substrate of numerous tyrosine kinases.
  • This discovery provides crucial insights into the molecular mechanisms of tyrosine kinase signaling and rasGAP regulation.

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