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.
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Acknowledgements
We thank Professor MD Resh and Drs DA Cantrell, J Ihle, Y Yamanashi for kindly providing reagents and Dr H-T He for helpful discussions. We are grateful to Marie-Claire and Peter Gerhards for the correction of the manuscript. This research was supported by the Institut National de la Santé et de la Recherche Médicale, by Grant 4330 from the Association pour la recherche contre le Cancer, by grants from the Canadian Institutes of Health Research (CIHR) to P Duplay and a grant ‘équipe labellisée 2001’ from the Ligue Nationale Contre le Cancer. C Favre was supported by a fellowship from the Association pour la recherche contre le Cancer. F Garçon was supported by a fellowship from the Ligue Nationale Contre le Cancer. P Duplay is a CIHR New Investigator.
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Gérard, A., Favre, C., Garçon, F. et al. Functional interaction of RasGAP-binding proteins Dok-1 and Dok-2 with the Tec protein tyrosine kinase. Oncogene 23, 1594–1598 (2004). https://doi.org/10.1038/sj.onc.1207283
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DOI: https://doi.org/10.1038/sj.onc.1207283
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