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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.

Original publication




Journal article



Publication Date





1594 - 1598


U119 INSERM, Institut de Cancérologie et d'Immunologie de Marseille, Université de la Méditerranée, 27 Bd Leï Roure, Marseille F-13009, France.


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