GPCRs Signaling Directly Through Src-Family Kinases

Sci. STKE, 26 June 2007
Vol. 2007, Issue 392, p. pe35
DOI: 10.1126/stke.3922007pe35

GPCRs Signaling Directly Through Src-Family Kinases

  1. Deirdre McGarrigle and
  2. Xin-Yun Huang*
  1. Department of Physiology, Cornell University Weill Medical College, New York, NY 10021, USA.
  1. *Corresponding author. E-mail, xyhuang{at}


A wide range of extracellular signals are transduced by G protein–coupled receptors (GPCRs). When activated by ligands, GPCRs can activate associated heterotrimeric guanine nucleotide–binding proteins (G proteins), which in turn act on various effectors. Increasing evidence indicates that GPCRs also signal independently of heterotrimeric G proteins. Several GPCRs directly interact with Src-family kinases. Here, we discuss the evidence for direct interaction and activation of Src-family kinases by GPCRs and data that suggest that agonist dosage provides a mechanism by which GPCRs can switch between G protein–dependent and G protein–independent signaling.


D. McGarrigle and X.-Y. Huang, GPCRs Signaling Directly Through Src-Family Kinases. Sci. STKE 2007, pe35 (2007).

Src family kinases: at the forefront of platelet activation
Y. A. Senis, A. Mazharian, and J. Mori
Blood 124, 2013-2024 (25 September 2014)

Endothelial Nitric-oxide Synthase (eNOS) Is Activated through G-protein-coupled Receptor Kinase-interacting Protein 1 (GIT1) Tyrosine Phosphorylation and Src Protein
S. Liu, R. T. Premont, and D. C. Rockey
J Biol Chem 289, 18163-18174 (27 June 2014)

Class I Phosphoinositide-3-Kinases and Src Kinases Play a Nonredundant Role in Regulation of Adhesion-Independent and -Dependent Neutrophil Reactive Oxygen Species Generation
L. Fumagalli, C. C. Campa, G. Germena, C. A. Lowell, E. Hirsch, and G. Berton
J. Immunol. 190, 3648-3660 (1 April 2013)

CD36 level and trafficking are determinants of lipolysis in adipocytes
D. Zhou, D. Samovski, A. L. Okunade, P. D. Stahl, N. A. Abumrad, and X. Su
FASEB J. 26, 4733-4742 (1 November 2012)

Src family kinases participate in the regulation of encephalomyocarditis virus-induced cyclooxygenase-2 expression by macrophages
W. Freudenburg, R. M. L. Buller, and J. A. Corbett
J. Gen. Virol. 91, 2278-2285 (1 September 2010)

Clostridium difficile toxin B differentially affects GPCR-stimulated Ca2+ responses in macrophages: independent roles for Rho and PLA2
R. A. Rebres, C. Moon, D. DeCamp, K. M. Lin, I. D. Fraser, S. B. Milne, T. I. A. Roach, H. A. Brown, and W. E. Seaman
J. Leukoc. Biol. 87, 1041-1057 (1 June 2010)

The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic {beta}-cell line
L. A. Swayne, A. Mezghrani, A. Varrault, J. Chemin, G. Bertrand, S. Dalle, E. Bourinet, P. Lory, R. J. Miller, J. Nargeot et al.
EMBO Rep. 10, 873-880 (1 August 2009)

Inhibition of Gluconeogenesis in Primary Hepatocytes by Stromal Cell-derived Factor-1 (SDF-1) through a c-Src/Akt-dependent Signaling Pathway
H.-Y. Liu, G.-B. Wen, J. Han, T. Hong, D. Zhuo, Z. Liu, and W. Cao
J Biol Chem 283, 30642-30649 (7 November 2008)

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882