Mediation by the protein-tyrosine kinase Tec of signaling between the B cell antigen receptor and Dok-1.

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.
Mesh Terms:
B-Lymphocytes, Burkitt Lymphoma, Cell Line, DNA-Binding Proteins, Humans, Nerve Tissue Proteins, Nuclear Proteins, Phosphoproteins, Phosphorylation, RNA-Binding Proteins, Receptors, Antigen, B-Cell, Receptors, Steroid, Receptors, Thyroid Hormone, Recombinant Fusion Proteins, Signal Transduction, Transfection, Tumor Cells, Cultured, Zinc Fingers, ras GTPase-Activating Proteins, src Homology Domains
J. Biol. Chem.
Date: Aug. 11, 2000
Download Curated Data For This Publication
158346
Switch View:
  • Interactions 9