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12-O-Tetradecanoylphorbol-13-acetate activates the Ras/extracellular signal-regulated kinase (ERK) signaling pathway upstream of SOS involving serine phosphorylation of Shc in NIH3T3 cells

Item Type:Article
Title:12-O-Tetradecanoylphorbol-13-acetate activates the Ras/extracellular signal-regulated kinase (ERK) signaling pathway upstream of SOS involving serine phosphorylation of Shc in NIH3T3 cells
Creators Name:El-Shemerly, M.Y. and Besser, D. and Nagasawa, M. and Nagamine, Y.
Abstract:We investigated the activation of the Ras/ERK signaling pathway by 12-O-tetradecanoylphorbol-13-acetate (TPA) in NIH3T3 fibroblasts. Interestingly, the activation was suppressed not only by dominant negative Raf-1 but also by dominant negative Ras and SOS. Further analysis revealed that TPA treatment induced, dependently on protein kinase C, the mobility shift of p66(shc) in SDS-polyacrylamide gel electrophoresis, which could be prevented by treatment of the Shc immunoprecipitate with serine/threonine-specific protein phosphatase 1 (PP1) or 2A (PP2A). Phosphoamino acid analysis of Shc showed that unlike growth factor-induced Shc phosphorylation, where Shc is mainly phosphorylated at tyrosine residues, TPA-induced phosphorylation was only at serine residues. Like growth factor-induced Shc phosphorylation, which leads to the association of Shc with Grb2, TPA also induced this association, but, correspondingly to the above results, the TPA-induced association was disrupted by in vitro treatment of the Shc immunoprecipitate with PP1. Taken together, these results suggest that the TPA signal was fed at or upstream of Shc to activate the Ras/ERK signaling pathway involving serine phosphorylation of Shc.
Keywords:3T3 Cells, Signal Transducing Adaptor Proteins, Vesicular Transport Adaptor Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Enzyme Activation, Fibroblast Growth Factor 2, Gene Expression Regulation, Isoenzymes, Mitogen-Activated Protein Kinases, Phosphorylation, Platelet-Derived Growth Factor, Protein Kinase C, Protein Kinase C-delta, Proteins, SOS Response (Genetics), Serine, Shc Signaling Adaptor Proteins, Signal Transduction, Tetradecanoylphorbol Acetate, Transcriptional Activation, ras Proteins, src Homology Domains, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:272
Number:49
Page Range:30599-30602
Date:5 December 1997
Official Publication:http://www.jbc.org/cgi/content/abstract/272/49/30599
PubMed:View item in PubMed

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