The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
The Function of GRB2 in Linking the Insulin Receptor to Ras Signaling Pathways
Abstract
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, a dominant negative form of Ras (with Ser 17 substituted with Asn) blocked insulin-induced activation of ERKs in cells that overexpressed GRB2. GRB2 overexpression led to increased formation of a complex between the guanine nucleotide-releasing factor Sos (the product of the mammalian homolog of son of sevenless gene) and GRB2. In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. In contrast to the activated epidermal growth factor receptor that binds the GRB2-Sos complex directly, activation of the insulin receptor results in the interaction of GRB2-Sos with IRS-1 and Shc, thus linking the insulin receptor to Ras signaling pathways.
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Cites
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The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling
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Self-citationStructure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
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Cited by
Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene
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Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1
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Self-citationProtein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistance
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Pendergast, A. M., Quilliam, L. A., Cripe, L. D., Bassing, C. H., Dai, Z., Li, N., Batzer, A., Rabun, K. M., Der, C. J., Schlessinger, J., et al. (1993) · Cell · doi:10.1016/0092-8674(93)90689-n · Cited by 659
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Metadata
- Authors
- Skolnik, E. Y., Batzer, A., Li, N., Lee, C.-H., Lowenstein, E., Mohammadi, M., Margolis, B., & Schlessinger, J.
- Venue
- Science
- Published
- 1993-06-25
- Volume
- 260
- Issue
- 5116
- Pages
- 1953-1955
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2089889881
- Cited by
- 632
- References
- 44
- FWCI
- 28.10
- Type
- journal article
- Language
- en
- Open access
- closed
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- Skolnik, E. Y., Batzer, A., Li, N., Lee, C.-H., Lowenstein, E., Mohammadi, M., Margolis, B., & Schlessinger, J. (1993). The Function of GRB2 in Linking the Insulin Receptor to Ras Signaling Pathways. Science. https://doi.org/10.1126/science.8316835
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