Publication Date:
1997-01-17
Description:
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 Gbetagamma subunits, but the subsequent intervening molecules are still poorly defined. Overexpression of phosphoinositide 3-kinase gamma (PI3Kgamma) in COS-7 cells activated MAPK in a Gbetagamma-dependent fashion, and expression of a catalytically inactive mutant of PI3Kgamma abolished the stimulation of MAPK by Gbetagamma or in response to stimulation of muscarinic (m2) G protein-coupled receptors. Signaling from PI3Kgamma to MAPK appears to require a tyrosine kinase, Shc, Grb2, Sos, Ras, and Raf. These findings indicate that PI3Kgamma mediates Gbetagamma-dependent regulation of the MAPK signaling pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lopez-Ilasaca, M -- Crespo, P -- Pellici, P G -- Gutkind, J S -- Wetzker, R -- New York, N.Y. -- Science. 1997 Jan 17;275(5298):394-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Research Unit Molecular Cell Biology, Medical Faculty, University of Jena, 07747 Jena, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8994038" target="_blank"〉PubMed〈/a〉
Keywords:
*Adaptor Proteins, Signal Transducing
;
Androstadienes/pharmacology
;
Animals
;
COS Cells
;
Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
;
Carbachol/pharmacology
;
Cell Membrane/enzymology
;
Enzyme Activation
;
GRB2 Adaptor Protein
;
GTP-Binding Proteins/*metabolism
;
Guanine Nucleotide Exchange Factors
;
Mitogen-Activated Protein Kinase 1
;
Phosphatidylinositol 3-Kinases
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Phosphorylation
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Phosphotransferases (Alcohol Group Acceptor)/*metabolism
;
Proteins/metabolism
;
Receptor Protein-Tyrosine Kinases/metabolism
;
Receptor, Muscarinic M2
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Receptors, Muscarinic/metabolism
;
Recombinant Fusion Proteins/metabolism
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*Signal Transduction
;
Transfection
;
Tyrosine/metabolism
;
ras Guanine Nucleotide Exchange Factors
;
ras Proteins/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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