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

被引:33
作者
Gérard, A
Favre, C
Garçon, F
Némorin, JG
Duplay, P
Pastor, S
Collette, Y
Olive, D
Nunès, JA
机构
[1] Univ Mediterranee, Inst Canc & Immunol Marseille, INSERM, U119, F-13009 Marseille, France
[2] Univ Quebec, Inst Armand Frappier, Inst Natl Rech Sci, Laval, PQ, Canada
基金
加拿大健康研究院;
关键词
Dok adaptor proteins; Tec tyrosine kinase; signal transduction; tumor suppressors; T cells;
D O I
10.1038/sj.onc.1207283
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1594 / 1598
页数:5
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