Related Experiment Video
Updated: Aug 16, 2026

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
Published on: January 23, 2018
Dominant negative farnesyltransferase alpha-subunit inhibits insulin mitogenic effects
1Research Service, Denver VA Medical Center, 1055 Clermont Street, Denver, CO 80220, USA.
Abstract:
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.
Related Concept Videos
Eukaryotic Transcription Inhibitors
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Insulin Secretory Vesicles
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
Diabetes Mellitus: Overview and Type I Subtype
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Insulin: The Receptor and Signaling Pathways
Type II Diabetes II: Pathophysiology

