Abstract
Heterotrimeric G proteins, consisting of the guanine nucleotide-binding Gα subunits with GTPase activity and the closely associated Gβ and Gγ subunits, are important signaling components for receptors with seven transmembrane domains (7TMRs). These receptors, also termed G protein-coupled receptors (GPCRs), act as guanine nucleotide exchange factors upon agonist stimulation. There is now accumulating evidence for noncanonical functions of heterotrimeric G proteins independent of 7TMR coupling. Gα proteins belonging to all 4 subfamilies, including Gs, Gi, Gq, and G12 are found to play important roles in receptor tyrosine kinase signaling, regulation of oxidant production, development, and cell migration, through physical and functional interaction with proteins other than 7TMRs. Association of Gα with non-7TMR proteins also facilitates presentation of these G proteins to specific cellular microdomains. This Minireview aims to summarize our current understanding of the noncanonical roles of Gα proteins in cell signaling and to discuss unresolved issues including regulation of Gα activation by proteins other than the 7TMRs.
Footnotes
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This work was supported in part by the National Institutes of Health National Institute of General Medical Sciences [Grant GM066182] and the National Institutes of Health National Institute of Allergy and Infectious Diseases Extramural Activities [Grant AI033503] (to R.D.Y.).
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Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
doi:10.1124/mol.110.063453.
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ABBREVIATIONS:
- 7TMR
- seven-transmembrane domain receptor
- GPCR
- G protein-coupled receptor
- GEF
- guanine nucleotide exchange factor
- JAK
- Janus kinase
- STAT
- signal transducer and activator of transcription
- AGS
- activators of G protein signaling
- TPR
- tetratricopeptide repeat
- RTK
- receptor tyrosine kinase
- EGF
- epidermal growth factor
- EGFR
- epidermal growth factor receptor
- PDGF
- platelet-derived growth factor
- IGF
- insulin-like growth factor
- PTX
- pertussis toxin
- mTORC1
- mammalian target of rapamycin complex 1
- Gab1
- Grb2-associated binding protein 1
- PI3K
- phosphatidylinositol 3-kinase
- EPO
- erythropoietin
- GM-CSF
- granulocyte macrophage-colony stimulating factor
- MAPK
- mitogen-activated protein kinase
- IL
- interleukin
- EPOR
- erythropoietin receptor
- AP-1
- activator protein 1
- TLR4
- Toll-like receptor 4.
- Received January 5, 2010.
- Accepted April 19, 2010.
- Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics
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