Functional interaction of RasGAP-binding proteins Dok-1 and Dok-2 with the Tec protein tyrosine kinase

Oncogene. 2004 Feb 26;23(8):1594-8. doi: 10.1038/sj.onc.1207283.

Abstract

The Dok adaptor family of proteins binding to RasGAP, consisting of Dok-1 and Dok-2, are critical regulators in cell proliferation. These molecules are partners and/or substrates of different protein tyrosine kinases considered as oncoproteins. Here, we show that Dok-1 and Dok-2 are the major tyrosine-phosphorylated proteins associated to Tec, a protein tyrosine kinase expressed in T cells. Furthermore, we evaluate the effect of Dok-1 or Dok-2 on Tec-mediated signalling pathways in T cells. Here, we provide evidence that Dok-1 and Dok-2 proteins are involved in a negative feedback regulation of Tec via a downregulation of its tyrosine phosphorylation and downstream signalling pathways including the Ras pathway. Either Dok-1 or Dok-2 therefore represents a mean of potent retrograde control for protein tyrosine kinase signalling, and then possibly of tumor development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Humans
  • Hybridomas / metabolism
  • Jurkat Cells
  • Mice
  • Mice, Knockout
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction
  • T-Lymphocytes / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • DOK1 protein, human
  • DOK2 protein, human
  • Dok1 protein, mouse
  • Dok2 protein, mouse
  • GAP-associated protein p62
  • Phosphoproteins
  • RNA-Binding Proteins
  • Tec protein-tyrosine kinase
  • Protein-Tyrosine Kinases