Insulin-induced p21ras activation does not require protein kinase C, but a protein sensitive to phenylarsine oxide

Insulin treatment of fibroblasts overexpressing the insulin receptor causes a rapid accumulation of the GTP-bound form of p21ras. We have studied the involvement of protein kinase C (PKC) in, and the effect of phenylarsine oxide (PAO), a putative inhibitor of tyrosine phosphatase activity on, this p...

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Bibliographic Details
Published in:The Journal of biological chemistry 1991-11, Vol.266 (31), p.21186-21189
Main Authors: Medema, R.H., Burgering, B.M., Bos, J.L.
Format: Article
Language:English
Subjects:
3T3 Cells
Analytical, structural and metabolic biochemistry
Animals
Arsenicals - pharmacology
Biological and medical sciences
Down-Regulation
Fundamental and applied biological sciences. Psychology
Gene Expression - drug effects
GTP-Binding Proteins - metabolism
Guanosine Triphosphate - metabolism
In Vitro Techniques
Insulin - pharmacology
Mice
Miscellaneous
phenylarsine oxide
Phosphorylation
Protein Kinase C - physiology
Proteins
Proto-Oncogene Proteins p21(ras) - genetics
Ras
Receptor, Insulin - physiology
Receptors, Antigen, T-Cell - physiology
Signal Transduction
Sulfhydryl Reagents - pharmacology
Tetradecanoylphorbol Acetate - pharmacology
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Summary:Insulin treatment of fibroblasts overexpressing the insulin receptor causes a rapid accumulation of the GTP-bound form of p21ras. We have studied the involvement of protein kinase C (PKC) in, and the effect of phenylarsine oxide (PAO), a putative inhibitor of tyrosine phosphatase activity on, this process. Activation of p21ras was not observed when the cells were stimulated with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and pretreatment with TPA for 16 h, sufficient to down-regulate PKC activity, did not abolish p21ras activation by insulin. These results show that PKC is not involved in the insulin-induced activation of p21ras. Pretreatment of the cells with PAO for 5 min completely blocked insulin-induced p21ras activation. Addition of 2,3-dimercaptopropanol prevented this inhibition by PAO. Also, addition of PAO after insulin stimulation could reverse the activation of p21ras. Since PAO did not affect overall phosphorylation of the insulin receptor beta-chain, we conclude that a PAO-sensitive protein is involved in the induction of p21ras activation by insulin.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)54838-9