title: Functional interaction of RasGAP-binding proteins Dok-1 and Dok-2 with the Tec protein tyrosine kinase.
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.
authors.affiliation: U119 INSERM, Institut de Cancérologie et d'Immunologie de Marseille, Université de la Méditerranée, 27 Bd Leï Roure, Marseille F-13009, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gérard
authors.forename: Cédric
authors.initials: C
authors.lastname: Favre
authors.forename: Fabien
authors.initials: F
authors.lastname: Garçon
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Némorin
authors.forename: Pascale
authors.initials: P
authors.lastname: Duplay
authors.forename: Sonia
authors.initials: S
authors.lastname: Pastor
authors.forename: Yves
authors.initials: Y
authors.lastname: Collette
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.forename: Jacques A
authors.initials: JA
authors.lastname: Nunès
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D019169:Jurkat Cells; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C489560:DOK1 protein, human; C115089:DOK2 protein, human; C489561:Dok1 protein, mouse; C498444:Dok2 protein, mouse; C074561:GAP-associated protein p62; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases