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Epidermal growth factor differentially augments G(i)-mediated stimulation of c-Jun N-terminal kinase activity.
Br J Pharmacol. 2004 Jun; 142(4):635-46.BJ

Abstract

1. Signaling networks involving different receptor systems allow extracellular signals to be integrated and transformed into various biological activities. In this report, we studied the activity of the c-Jun N-terminal kinase (JNK) subgroup of mitogen-activated protein kinases (MAPKs), in response to stimulation by G protein-coupled receptors (GPCRs) and co-activation with epithermal growth factor receptor (EGFR). 2. Stimulation of exogenous GPCRs in Cos-7 cells induced JNK activation of different magnitudes depending on their G-protein coupling specificities (G(q)>G(i)>G(s)), and a moderate JNK activation was linked to stimulation of endogenous EGFR by EGF. 3. Co-stimulation with GPCR agonists and EGF resulted in differential augmentation of JNK activities, with G(i)-coupled receptors associated with a synergistic JNK activation upon co-stimulation with EGF, while G(q)- and G(s)-coupled receptors were incapable of triggering this effect. 4. This G(i)/EGF-induced synergistic JNK activation was inhibited by pertussis toxin and AG1478, and may involve Src family tyrosine kinases, PI3 K, Ca(2+)/calmodulin and small GTPases as important intermediates, while Ca(2+) mobilization was triggered by the stimulation of G(q)-coupled receptor or EGF treatment, but not by the G(i)- or G(s)-coupled receptors. 5. Transient expression of Gbetagamma subunits with EGF treatment, or co-activation of exogenous G(i)-coupled receptor with thapsigargin also resulted in a synergistic JNK activation. Activation of G(i)-coupled receptor accompanied with EGF treatment enhanced the expression level and activity of MAPK phosphatase type I, which occurred after the maximal synergistic JNK activation. 6. Our results support a mechanistic model where EGF signaling may differentially regulate the JNK activities triggered by GPCRs of different coupling specificities.

Authors+Show Affiliations

Department of Biochemistry, The Biotechnology Research Institute, and The Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong. boyung@ust.hkNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15172963

Citation

Chan, Anthony S L., and Yung H. Wong. "Epidermal Growth Factor Differentially Augments G(i)-mediated Stimulation of c-Jun N-terminal Kinase Activity." British Journal of Pharmacology, vol. 142, no. 4, 2004, pp. 635-46.
Chan AS, Wong YH. Epidermal growth factor differentially augments G(i)-mediated stimulation of c-Jun N-terminal kinase activity. Br J Pharmacol. 2004;142(4):635-46.
Chan, A. S., & Wong, Y. H. (2004). Epidermal growth factor differentially augments G(i)-mediated stimulation of c-Jun N-terminal kinase activity. British Journal of Pharmacology, 142(4), 635-46.
Chan AS, Wong YH. Epidermal Growth Factor Differentially Augments G(i)-mediated Stimulation of c-Jun N-terminal Kinase Activity. Br J Pharmacol. 2004;142(4):635-46. PubMed PMID: 15172963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epidermal growth factor differentially augments G(i)-mediated stimulation of c-Jun N-terminal kinase activity. AU - Chan,Anthony S L, AU - Wong,Yung H, Y1 - 2004/06/01/ PY - 2004/6/3/pubmed PY - 2005/1/26/medline PY - 2004/6/3/entrez SP - 635 EP - 46 JF - British journal of pharmacology JO - Br J Pharmacol VL - 142 IS - 4 N2 - 1. Signaling networks involving different receptor systems allow extracellular signals to be integrated and transformed into various biological activities. In this report, we studied the activity of the c-Jun N-terminal kinase (JNK) subgroup of mitogen-activated protein kinases (MAPKs), in response to stimulation by G protein-coupled receptors (GPCRs) and co-activation with epithermal growth factor receptor (EGFR). 2. Stimulation of exogenous GPCRs in Cos-7 cells induced JNK activation of different magnitudes depending on their G-protein coupling specificities (G(q)>G(i)>G(s)), and a moderate JNK activation was linked to stimulation of endogenous EGFR by EGF. 3. Co-stimulation with GPCR agonists and EGF resulted in differential augmentation of JNK activities, with G(i)-coupled receptors associated with a synergistic JNK activation upon co-stimulation with EGF, while G(q)- and G(s)-coupled receptors were incapable of triggering this effect. 4. This G(i)/EGF-induced synergistic JNK activation was inhibited by pertussis toxin and AG1478, and may involve Src family tyrosine kinases, PI3 K, Ca(2+)/calmodulin and small GTPases as important intermediates, while Ca(2+) mobilization was triggered by the stimulation of G(q)-coupled receptor or EGF treatment, but not by the G(i)- or G(s)-coupled receptors. 5. Transient expression of Gbetagamma subunits with EGF treatment, or co-activation of exogenous G(i)-coupled receptor with thapsigargin also resulted in a synergistic JNK activation. Activation of G(i)-coupled receptor accompanied with EGF treatment enhanced the expression level and activity of MAPK phosphatase type I, which occurred after the maximal synergistic JNK activation. 6. Our results support a mechanistic model where EGF signaling may differentially regulate the JNK activities triggered by GPCRs of different coupling specificities. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/15172963/Epidermal_growth_factor_differentially_augments_G_i__mediated_stimulation_of_c_Jun_N_terminal_kinase_activity_ L2 - https://doi.org/10.1038/sj.bjp.0705851 DB - PRIME DP - Unbound Medicine ER -