What question did this study set out to answer?

To determine how the adaptor protein GRB2 connects activated insulin receptors to downstream Ras and ERK signaling pathways.

June 25, 1993Science

The Function of GRB2 in Linking the Insulin Receptor to Ras Signaling Pathways

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Authors

ESE. Y. SkolnikNYU Langone Health ABAndreas BatzerSanofi (Germany)NLNanxin LiDartmouth College

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Overview

In vitro study demonstrates GRB2-mediated coupling of insulin receptors to Ras signaling via IRS-1 and Shc in cell cultures, indicating an indirect recruitment pathway for MAPK activation.

Key Points

To determine how the adaptor protein GRB2 connects activated insulin receptors to downstream Ras and ERK signaling pathways.
Stably overexpressed wild-type GRB2 or mutant variants containing point mutations in the SH2 and SH3 domains in cell lines.
Assessed insulin-induced ERK activation in the presence of dominant-negative Ras (Ser17Asn) and analyzed protein complex formation between GRB2, Sos, IRS-1, and Shc.
Wild-type GRB2 overexpression enhanced insulin-induced activation of ERKs, whereas GRB2 variants with SH2 or SH3 point mutations failed to enhance activation.
Dominant-negative Ras completely blocked insulin-induced ERK activation in cells overexpressing GRB2.
GRB2 formed a complex with the guanine nucleotide-releasing factor Sos that bound to tyrosine-phosphorylated IRS-1 and Shc upon insulin stimulation, rather than binding directly to the insulin receptor.

Cite This Study

Skolnik et al. (1993) studied this question.

synapsesocial.com/papers/6a659febf3bdf71dcbd6a074 https://doi.org/10.1126/science.8316835

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June 25, 1993Science

The Function of GRB2 in Linking the Insulin Receptor to Ras Signaling Pathways

View Full Paper

Ask AI

Bookmark

Authors

ESE. Y. SkolnikNYU Langone Health ABAndreas BatzerSanofi (Germany)NLNanxin LiDartmouth College

Discussion

Member takes

Overview

In vitro study demonstrates GRB2-mediated coupling of insulin receptors to Ras signaling via IRS-1 and Shc in cell cultures, indicating an indirect recruitment pathway for MAPK activation.

Key Points

To determine how the adaptor protein GRB2 connects activated insulin receptors to downstream Ras and ERK signaling pathways.
Stably overexpressed wild-type GRB2 or mutant variants containing point mutations in the SH2 and SH3 domains in cell lines.
Assessed insulin-induced ERK activation in the presence of dominant-negative Ras (Ser17Asn) and analyzed protein complex formation between GRB2, Sos, IRS-1, and Shc.
Wild-type GRB2 overexpression enhanced insulin-induced activation of ERKs, whereas GRB2 variants with SH2 or SH3 point mutations failed to enhance activation.
Dominant-negative Ras completely blocked insulin-induced ERK activation in cells overexpressing GRB2.
GRB2 formed a complex with the guanine nucleotide-releasing factor Sos that bound to tyrosine-phosphorylated IRS-1 and Shc upon insulin stimulation, rather than binding directly to the insulin receptor.

Cite This Study

Skolnik et al. (1993) studied this question.

synapsesocial.com/papers/6a659febf3bdf71dcbd6a074 https://doi.org/10.1126/science.8316835

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