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Cooperative mitogenic signaling by G protein‐coupled receptors and growth factors is dependent on G q/11
Author(s) -
Kong Kok Choi,
Billington Charlotte K.,
Gandhi Uma,
Panettieri Reynold A.,
Penn Raymond B.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-5622fje
Subject(s) - receptor , microbiology and biotechnology , chemistry , g protein coupled receptor , biology , biochemistry
Previously we reported that the G protein‐coupled receptor (GPCR) agonist thrombin potentiated the mitogenic effect of epidermal growth factor (EGF) on human airway smooth muscle (ASM) by promoting sustained late‐phase activation of PI3K and p70S6K via a pathway dependent on Gβγ subunits of heterotrimeric G proteins. Here, we provide additional mechanistic insight and reveal the robustness of this phenomenon by demonstrating that H1 histamine and thromboxane receptors utilize the same mechanism to augment ASM growth via specific activation of the heterotrimeric G protein G q/11 . Thrombin, histamine, and U46619 all enhanced EGF‐stimulated [ 3 H]‐thymidine incorporation as well as late‐phase Akt and p70S6K phosphorylation in ASM cultures. Heterologous expression of Gβγ sequestrants (GRK2CT‐GFP or Gα i G203A), as well as GRK2NT‐GFP (an RGS protein for G q/11 ) but neither p115RhoGEFRGS‐GFP (an RGS for G 12/13 ) nor pertussis toxin pretreatment (inactivating G i/o ), attenuated the effects on both signaling and growth. Inhibition of Rho, Rho kinase, or Src, or modulation of arrestin expression did not significantly affect the cooperative signaling by EGF and any of the GPCR agonists. Thus, G q/11 ‐coupled receptors are the principal GPCR subfamily mediating cooperative mitogenic signaling in ASM, acting through Gβγ‐dependent, and Src/arrestin‐independent activation of PI3K and p70S6K.—Kong, K. C., Billington, C. K., Gandhi, U., Panettieri, R. A., Penn, R. B. Cooperative mitogenic signaling by G protein‐coupled receptors and growth factors is dependent on G q/11 . FASEB J. 20, E880–E887 (2006)