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Linkage of G Protein-Coupled Receptors to the MAPK Signaling Pathway Through PI 3-Kinase γ
Abstract
The tyrosine kinase class of receptors induces mitogen-activated protein kinase (MAPK) activation through the sequential interaction of the signaling proteins Grb2, Sos, Ras, Raf, and MEK. Receptors coupled to heterotrimeric guanine triphosphate-binding protein (G protein) stimulate MAPK through G β γ subunits, but the subsequent intervening molecules are still poorly defined. Overexpression of phosphoinositide 3-kinase γ (PI3Kγ) in COS-7 cells activated MAPK in a G β γ -dependent fashion, and expression of a catalytically inactive mutant of PI3Kγ abolished the stimulation of MAPK by G β γ or in response to stimulation of muscarinic (m2) G protein-coupled receptors. Signaling from PI3Kγ to MAPK appears to require a tyrosine kinase, Shc, Grb2, Sos, Ras, and Raf. These findings indicate that PI3Kγ mediates G β γ -dependent regulation of the MAPK signaling pathway.
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Metadata
- Authors
- Lopez-Ilasaca, M., Crespo, P., Pellici, P. G., Gutkind, J. S., & Wetzker, R.
- Venue
- Science
- Published
- 1997-01-17
- Volume
- 275
- Issue
- 5298
- Pages
- 394-397
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2092014913
- Cited by
- 670
- References
- 0
- FWCI
- 28.46
- Type
- journal article
- Language
- en
- Open access
- closed
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- Lopez-Ilasaca, M., Crespo, P., Pellici, P. G., Gutkind, J. S., & Wetzker, R. (1997). Linkage of G Protein-Coupled Receptors to the MAPK Signaling Pathway Through PI 3-Kinase γ. Science. https://doi.org/10.1126/science.275.5298.394
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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