Mitogen-stimulated tyrosine phosphorylation of a 42-kD cellular protein: evidence for a protein kinase-C requirement.
Tyrosine phosphorylation of a 42-kD, cytosolic protein is a rapid consequence when quiescent cells are stimulated with any one of a diverse group of mitogenic agents. Among the inducers of this tyrosine phosphorylation are activators of protein kinase C, raising the possibility that this serine/threonine-specific protein kinase plays a role in mitogen-induced tyrosine phosphorylation. Using fibroblastic cells depleted of protein kinase C by chronic treatment with the tumor promoter tetradecanoyl phorbol acetate (TPA), we now show that protein kinase C is required for the tyrosine phosphorylation of the 42-kD protein, even when epidermal growth factor (EGF), whose receptor is a tyrosine-specific protein kinase, provides the initial stimulus. EGF is able to induce other cellular phosphorylations independent of protein kinase C, whereas thrombin appears to require the protein kinase C-dependent pathway. These findings suggest that phosphorylation of the 42-kD protein is part of a protein kinase C-dependent kinase cascade involved in intracellular signalling.
Vila
J
J
Department of Microbiology, University of Virginia School of Medicine, Charlottesville 22908.
Weber
M J
MJ
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D008934:Mitogens; D008970:Molecular Weight; D010710:Phosphates / Q000378:metabolism; D010750:Phosphoproteins / Q000302:isolation & purification; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D014443:Tyrosine
D008934:Mitogens; D010710:Phosphates; D010750:Phosphoproteins; D010761:Phosphorus Radioisotopes; D011506:Proteins; D014443:Tyrosine; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate