Mediation by the protein-tyrosine kinase Tec of signaling between the B cell antigen receptor and Dok-1.
J Biol Chem
; 275(32): 24945-52, 2000 Aug 11.
Article
em En
| MEDLINE
| ID: mdl-10823839
ABSTRACT
A variety of growth factor receptors induce the tyrosine phosphorylation of a nonreceptor protein-tyrosine kinase Tec as well as that of a Tec-binding protein of 62 kDa. Given the similarity in properties between this 62-kDa protein and p62(Dok-1), the possibility that these two proteins are identical was investigated. Overexpression of a constitutively active form of Tec in a pro-B cell line induced the hyperphosphorylation of endogenous Dok-1. Tec also associated with Dok-1 in a phosphorylation-dependent manner in 293 cells. Tec mediated marked phosphorylation of Dok-1 both in vivo and in vitro, and this effect required both the Tec homology and Src homology 2 domains of Tec in addition to its kinase activity. Expression of Dok-1 in 293 cells induced inhibition of Ras activity, suggesting that Dok-1 is a negative regulator of Ras. In the immature B cell line Ramos, cross-linking of the B cell antigen receptor (BCR) resulted in tyrosine phosphorylation of Dok-1, and this effect was markedly inhibited by expression of dominant negative mutants of Tec. Furthermore, overexpression of Dok-1 inhibited activation of the c-fos promoter induced by stimulation of the BCR. These results suggest that Tec is an important mediator of signaling from the BCR to Dok-1.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Proteínas Nucleares
/
Receptores de Antígenos de Linfócitos B
/
Proteínas de Ligação a RNA
/
Proteínas de Ligação a DNA
/
Proteínas do Tecido Nervoso
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Japão