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Review ArticleMINIREVIEWS

Heterotrimeric G Protein Signaling Outside the Realm of Seven Transmembrane Domain Receptors

Caroline Marty and Richard D. Ye
Molecular Pharmacology July 2010, 78 (1) 12-18; DOI: https://doi.org/10.1124/mol.110.063453
Caroline Marty
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Richard D. Ye
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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

  • 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.).

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.110.063453.

  • 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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Molecular Pharmacology: 78 (1)
Molecular Pharmacology
Vol. 78, Issue 1
1 Jul 2010
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Review ArticleMINIREVIEWS

Heterotrimeric G Protein Signaling Outside the Realm of Seven Transmembrane Domain Receptors

Caroline Marty and Richard D. Ye
Molecular Pharmacology July 1, 2010, 78 (1) 12-18; DOI: https://doi.org/10.1124/mol.110.063453

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Review ArticleMINIREVIEWS

Heterotrimeric G Protein Signaling Outside the Realm of Seven Transmembrane Domain Receptors

Caroline Marty and Richard D. Ye
Molecular Pharmacology July 1, 2010, 78 (1) 12-18; DOI: https://doi.org/10.1124/mol.110.063453
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