Effect of insulin on farnesyltransferase. Specificity of insulin action and potentiation of nuclear effects of insulin-like growth factor-1, epidermal growth factor, and platelet-derived growth factor.
J Biol Chem
; 273(37): 23892-6, 1998 Sep 11.
Article
in En
| MEDLINE
| ID: mdl-9727002
ABSTRACT
We have previously demonstrated that insulin activates farnesyltransferase (FTase) and augments the amounts of farnesylated p21 (Goalstone, M. L., and Draznin, B. (1996) J. Biol. Chem. 271, 27585-27589). We postulated that this aspect of insulin action might explain the "priming effect" of insulin on the cellular response to other growth factors. In the present study, we show the specificity of the effect of insulin on FTase. Insulin, but not insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), or platelet-derived growth factor (PDGF), stimulated the phosphorylation of the alpha-subunit of FTase and the amounts of farnesylated p21. Even though all four growth factors utilized the Ras pathway to stimulate DNA synthesis, only insulin used this pathway to influence FTase. Insulin failed to stimulate FTase in cells expressing the chimeric insulin/IGF-1 receptor and in cells derived from the insulin receptor knock-out animals. Insulin potentiated the effects of IGF-1, EGF, and PDGF on DNA synthesis in cells expressing the wild type insulin receptor, but this potentiation was inhibited in the presence of the FTase inhibitor, alpha-hydroxyfarnesylphosphonic acid. We conclude that the effect of insulin on FTase is specific, requires the presence of an intact insulin receptor, and serves as a conduit for the "priming" influence of insulin on the nuclear effects of other growth factors.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Platelet-Derived Growth Factor
/
Insulin-Like Growth Factor I
/
Receptor, Insulin
/
Proto-Oncogene Proteins p21(ras)
/
Receptor, IGF Type 1
/
Alkyl and Aryl Transferases
/
Epidermal Growth Factor
/
Insulin
Limits:
Animals
Language:
En
Journal:
J Biol Chem
Year:
1998
Document type:
Article
Affiliation country:
United States