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Updated: Aug 29, 2026

Inducible and Reversible Dominant-negative (DN) Protein Inhibition
08:35

Inducible and Reversible Dominant-negative (DN) Protein Inhibition

Published on: January 7, 2019

Two dominant inhibitory mutants of p21ras interfere with insulin-induced gene expression

R H Medema1, R Wubbolts, J L Bos

  • 1Department of Physiological Chemistry, University of Utrecht, The Netherlands.

Molecular and Cellular Biology
|December 1, 1991
PubMed

Insights

Insulin rapidly activates p21ras, a key signaling molecule. This study demonstrates that p21ras acts as an intermediate in insulin-induced gene expression, mediating the signaling pathway.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Endocrinology

Background:

  • Insulin receptor signaling is crucial for cellular functions.
  • p21ras (RAS oncogene family) is implicated in various cellular processes.
  • Previous studies suggested a role for p21ras in insulin-induced gene expression.

Purpose of the Study:

  • To directly investigate the role of p21ras in insulin-induced gene expression.
  • To determine if dominant inhibitory mutants of p21ras can block insulin's effects on gene expression.

Main Methods:

  • NIH 3T3 cells overexpressing the insulin receptor were used.
  • Transfection with reporter gene constructs (collagenase promoter-CAT or fos promoter-luciferase).
  • Treatment with insulin and cotransfection with dominant inhibitory ras mutants (H-ras(Asn-17) or H-ras(Leu-61,Ser-186)).

Main Results:

  • Insulin treatment strongly induced both collagenase and fos promoter activities.
  • Cotransfection with inhibitory ras mutants suppressed insulin-induced promoter activation.
  • H-ras(Asn-17) completely inhibited insulin-induced fos promoter activation.

Conclusions:

  • p21ras functions as a critical intermediate in the insulin signal transduction pathway.
  • The RAS signaling pathway is essential for insulin-mediated gene induction.
  • These findings elucidate a key mechanism in insulin's cellular effects.

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