farnesyl-pyrophosphate and Hyperinsulinism

farnesyl-pyrophosphate has been researched along with Hyperinsulinism* in 1 studies

Other Studies

1 other study(ies) available for farnesyl-pyrophosphate and Hyperinsulinism

Article	Year
Dominant negative farnesyltransferase alpha-subunit inhibits insulin mitogenic effects. Biochemical and biophysical research communications, 2001, Jul-13, Volume: 285, Issue:2 Farnesylation of p21Ras is required for translocation to the plasma membrane and subsequent activation by growth factors. Previously we demonstrated that insulin stimulates the phosphorylation of farnesyltransferase (FTase) and its activity, whereby the amount of farnesylated p21Ras anchored at the plasma membrane is increased. Herein we report that substitution of alanine for two serine residues (S60A)(S62A) of the alpha-subunit of FTase creates a dominant negative (DN) mutant. VSMC expressing the FTase alpha-subunit (S60A)(S62A) clone showed a 30% decreased basal FTase activity concurrent with a 15% decrease in the amount of farnesylated p21Ras compared to controls. Expression of alpha-subunit (S60A,S62A) blunted FTase phosphorylation and activity in the presence of hyperinsulinemia, and inhibited insulin-stimulated increases in farnesylated p21Ras. Insulin-stimulated VSMC expressing the FTase alpha-subunit (S60A,S62A) showed decreased (i) phosphorylation of FTase, (ii) FTase activity, (iii) amounts of farnesylated p21Ras, (iv) DNA synthesis, and (v) migration. Thus, down-regulation of FTase activity appears to mitigate the potentially detrimental mitogenic effects of hyperinsulinemia on VSMC. Topics: Alkyl and Aryl Transferases; Amino Acid Sequence; Amino Acid Substitution; Animals; Cell Division; Cell Movement; Cells, Cultured; Cloning, Molecular; Farnesyltranstransferase; Hyperinsulinism; Insulin; Muscle, Smooth, Vascular; Phosphates; Phosphorylation; Platelet-Derived Growth Factor; Polyisoprenyl Phosphates; Protein Prenylation; Protein Subunits; Proto-Oncogene Proteins p21(ras); Recombinant Proteins; Sesquiterpenes; Transfection	2001

Article

Year

Dominant negative farnesyltransferase alpha-subunit inhibits insulin mitogenic effects.

Biochemical and biophysical research communications, 2001, Jul-13, Volume: 285, Issue:2

Farnesylation of p21Ras is required for translocation to the plasma membrane and subsequent activation by growth factors. Previously we demonstrated that insulin stimulates the phosphorylation of farnesyltransferase (FTase) and its activity, whereby the amount of farnesylated p21Ras anchored at the plasma membrane is increased. Herein we report that substitution of alanine for two serine residues (S60A)(S62A) of the alpha-subunit of FTase creates a dominant negative (DN) mutant. VSMC expressing the FTase alpha-subunit (S60A)(S62A) clone showed a 30% decreased basal FTase activity concurrent with a 15% decrease in the amount of farnesylated p21Ras compared to controls. Expression of alpha-subunit (S60A,S62A) blunted FTase phosphorylation and activity in the presence of hyperinsulinemia, and inhibited insulin-stimulated increases in farnesylated p21Ras. Insulin-stimulated VSMC expressing the FTase alpha-subunit (S60A,S62A) showed decreased (i) phosphorylation of FTase, (ii) FTase activity, (iii) amounts of farnesylated p21Ras, (iv) DNA synthesis, and (v) migration. Thus, down-regulation of FTase activity appears to mitigate the potentially detrimental mitogenic effects of hyperinsulinemia on VSMC.

Topics: Alkyl and Aryl Transferases; Amino Acid Sequence; Amino Acid Substitution; Animals; Cell Division; Cell Movement; Cells, Cultured; Cloning, Molecular; Farnesyltranstransferase; Hyperinsulinism; Insulin; Muscle, Smooth, Vascular; Phosphates; Phosphorylation; Platelet-Derived Growth Factor; Polyisoprenyl Phosphates; Protein Prenylation; Protein Subunits; Proto-Oncogene Proteins p21(ras); Recombinant Proteins; Sesquiterpenes; Transfection

2001