Mitogenic activation of the Ras guanine nucleotide exchange factor in NIH 3T3 cells involves protein tyrosine phosphorylation.
AUTOR(ES)
Li, B Q
RESUMO
We report biochemical evidence that epidermal growth factor and platelet-derived growth factor stimulate the Ras guanine nucleotide exchange factor activity in quiescent NIH 3T3 cells. Moreover, the exchange activity is constitutively enhanced in NIH 3T3 cells transformed by Src and ErbB2 oncogenic tyrosine protein kinases (TPKs), whereas transformation by oncogenic Mos and Raf does not alter the activity. GTPase-activating protein activity was not affected under these conditions. Overexpression of pp60c-Src mutants containing activated and suppressor TPK mutations resulted in stimulation and inhibition of the exchange factor activity, respectively. A TPK inhibitor, genistein, prevented the activation of the exchange factor in epidermal growth factor/platelet-derived growth factor-treated cells and src-transformed cells. Furthermore, the exchange factor activity bound to an anti-phosphotyrosine antibody immunoaffinity column. These findings suggest that the guanine nucleotide exchange factor, but not GTPase-activating protein, plays a major role in the Ras activation in cell proliferation initiated by growth factor receptor TPKs and malignant transformation by oncogenic TPKs and that tyrosine phosphorylation of either the exchange factor or a tightly bound protein(s) may mediate the activation of the exchange factor by these TPKs.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=47385Documentos Relacionados
- Platelet-derived growth factor stimulation of GTPase-activating protein tyrosine phosphorylation in control and c-H-ras-expressing NIH 3T3 cells correlates with p21ras activation.
- Heparin-binding growth factor 1 stimulates tyrosine phosphorylation in NIH 3T3 cells.
- Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells.
- Alteration of glycolipids in ras-transfected NIH 3T3 cells.
- Activation of the mitogen-activated protein kinase pathway in Triton X-100 disrupted NIH-3T3 cells by p21 ras and in vitro by plasma membranes from NIH 3T3 cells.