Related Experiment Videos
Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes
K Baltensperger1, L M Kozma, A D Cherniack
1Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605.
Abstract:
Signal transmission by insulin involves tyrosine phosphorylation of a major insulin receptor substrate (IRS-1) and exchange of Ras-bound guanosine diphosphate for guanosine triphosphate. Proteins containing Src homology 2 and 3 (SH2 and SH3) domains, such as the p85 regulatory subunit of phosphatidylinositol-3 kinase and growth factor receptor-bound protein 2 (GRB2), bind tyrosine phosphate sites on IRS-1 through their SH2 regions. Such complexes in COS cells were found to contain the heterologously expressed putative guanine nucleotide exchange factor encoded by the Drosophila son of sevenless gene (dSos). Thus, GRB2, p85, or other proteins with SH2-SH3 adapter sequences may link Sos proteins to IRS-1 signaling complexes as part of the mechanism by which insulin activates Ras.
Insights
Insulin signaling activates Ras through tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). Proteins with SH2 domains link IRS-1 to Sos proteins, mediating insulin
Area of Science:
- Molecular biology
- Cell signaling
- Biochemistry
Background:
- Insulin signaling is crucial for glucose metabolism and cellular growth.
- Key components include insulin receptor substrate-1 (IRS-1) and Ras.
- The precise mechanism linking IRS-1 to Ras activation is under investigation.
Purpose of the Study:
- To elucidate the role of specific proteins in mediating insulin signal transmission to Ras.
- To identify the interactions between IRS-1 and guanine nucleotide exchange factors.
Main Methods:
- Utilized COS cells for heterologous expression.
- Investigated protein-protein interactions involving IRS-1, SH2/SH3 domain proteins, and Sos.
- Analyzed tyrosine phosphorylation events in insulin signaling.
Main Results:
- Proteins with Src homology 2 (SH2) domains, like p85 and GRB2, bind to tyrosine-phosphorylated IRS-1.
- These complexes were found to associate with Drosophila son of sevenless (dSos), a guanine nucleotide exchange factor.
- This suggests a pathway linking IRS-1 to Sos proteins.
Conclusions:
- GRB2, p85, and similar adapter proteins may bridge Sos to IRS-1 signaling complexes.
- This linkage is proposed as a mechanism for insulin-induced Ras activation.
- The findings provide insight into the molecular events downstream of the insulin receptor.