The function of GRB2 in linking the insulin receptor to Ras signaling pathways.

@article{Skolnik1993TheFO,
  title={The function of GRB2 in linking the insulin receptor to Ras signaling pathways.},
  author={Edward Y Skolnik and Andreas Batzer and N Li and C H Lee and E. Lowenstein and Moosa Mohammadi and Ben L Margolis and Joseph Schlessinger},
  journal={Science},
  year={1993},
  volume={260 5116},
  pages={
          1953-5
        }
}
Insulin-induced activation of extracellular signal-regulated kinases [ERKs, also known as mitogen-activated protein (MAP) kinases] is mediated by Ras. Insulin activates Ras primarily by increasing the rate of guanine nucleotide-releasing activity. Here, we show that insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains. Moreover… 
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TLDR
The results suggest that the Shc-GRB-2 complex and the activation of p21ras-dependent signaling pathways, including MAP kinase, are insufficient for insulin-stimulated mitogenesis and that the essential function(s) of IRS-1 in proliferative signaling is largely unrelated to taxonomic formation.
Epidermal Growth Factor Receptor Targeting Prevents Uncoupling of the Grb2-SOS Complex (*)
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It is demonstrated that EGF stimulation prevents the feedback uncoupling of Grb2 from SOS by inducing a persistent plasma membrane receptor targeting of the Grb 2-SOS complex.
Association between GRB2/Sos and insulin receptor substrate 1 is not sufficient for activation of extracellular signal-regulated kinases by interleukin-4: implications for Ras activation by insulin.
TLDR
These findings suggest that binding of GRB2/Sos to Shc may be the predominant mechanism whereby insulin as well as cytokine receptors activate Ras, and ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex.
A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor tyrosine kinase
TLDR
The results indicate that GRB2 interacts with different growth factor receptors by different mechanisms and the cytoplasmic phosphotyrosine phosphatase Syp acts as an adapter between the PDGF receptor and the GRB 2-Sos complex.
Insulin Receptor-mediated Dissociation of Grb2 from Sos Involves Phosphorylation of Sos by Kinase(s) Other than Extracellular Signal-regulated Kinase*
TLDR
The causal relationship between Sos phosphorylated and Grb2/Sos dissociation is confirmed and several putative phosphorylation sites of Sos are examined that could potentially regulate this event.
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TLDR
It is concluded that Gabl is a new protein in EGF and insulin receptor signalling which could integrate signals from different systems and enhances cell growth and results in transformation.
Activation of Ras by receptor tyrosine kinases.
  • B. Margolis, E. Skolnik
  • Biology, Computer Science
    Journal of the American Society of Nephrology : JASN
  • 1994
TLDR
A combination of genetic and biochemical studies has resulted in the elucidation of a signaling pathway that leads from growth factor receptors to Ras, which proceeds to stimulate a cascade of protein kinases that are important in a myriad of growth factor responses.
A Lipid-Anchored Grb2-Binding Protein That Links FGF-Receptor Activation to the Ras/MAPK Signaling Pathway
Insulin and Epidermal Growth Factor Receptors Regulate Distinct Pools of Grb2-SOS in the Control of Ras Activation*
TLDR
Data suggest the presence of distinct Grb2-SOS pools that are independently utilized by insulin and EGF in their recruitment to tyrosine-phosphorylated Shc.
Differential effects of ethanol on insulin-signaling through the insulin receptor substrate-1.
TLDR
The findings suggest that insulin-stimulated DNA synthesis and PCNA expression are mediated through the Syp-binding domain, whereas GAPDH expression and MAPK activation are modulated through both the Grb2 and Syp motifs of IRS-1.
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References

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TLDR
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TLDR
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