Tyrosine phosphorylation in cells treated with transforming growth factor-beta.

Cells stimulated with epidermal growth factor (EGF) or any one of a diverse group of other mitogenic agents display an increased tyrosine phosphorylation of a pair of 42,000 Mr proteins. Transforming Growth Factor-beta (TGF-beta) is able to potentiate the mitogenic effects of Epidermal Growth Factor on some fibroblastic cells (such as the NRK-49F cell line) and, in addition, permits the anchorage-independent growth of these cells. In this study we asked whether these growth-regulatory actions of Transforming Growth Factor-beta are associated with changes in tyrosine phosphorylation of cellular proteins, in particular the 42,000 Mr proteins. We found no effect of Transforming Growth Factor-beta on the extent or time-course of tyrosine phosphorylation, either by itself or in combination with Epidermal Growth Factor. Since the tyrosine phosphorylation of the 42,000 Mr proteins is stimulated both by receptors with tyrosine kinase activity and by diacylglycerol analogs (but not by Transforming Growth Factor-beta), we suggest that the activity of the receptor for Transforming Growth Factor-beta is linked neither to tyrosine phosphorylation nor to phosphatidyl inositol turnover.