TY - JOUR
T1 - Regulation of α 2B-adrenergic receptor-mediated extracellular signal-regulated kinase 1/2 (ERK1/2) activation by ADP-ribosylation factor 1
AU - Dong, Chunmin
AU - Li, Chunman
AU - Wu, Guangyu
PY - 2011/12/16
Y1 - 2011/12/16
N2 - A number of signaling molecules are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway by G protein-coupled receptors. In this study, we have demonstrated that α 2B-adrenergic receptor (α 2B-AR) interacts with ADP-ribosylation factor 1 (ARF1), a small GTPase involved in vesicle-mediated trafficking, in an agonist activation-dependent manner and that the interaction is mediated through a unique double Trp motif in the third intracellular loop of the receptor. Interestingly, mutation of the double Trp motif and siRNA-mediated depletion of ARF1 attenuate α 2B-AR-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) without altering receptor intracellular trafficking, whereas expression of the constitutively active mutant ARF1Q71L and ARNO, a GDP-GTP exchange factor of ARF1, markedly enhances the activation of Raf1, MEK1, and ERK1/2. These data strongly demonstrate that the small GTPase ARF1 modulates ERK1/2 activation by α 2B-AR and provide the first evidence indicating a novel function for ARF1 in regulating the MAPK signaling pathway.
AB - A number of signaling molecules are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway by G protein-coupled receptors. In this study, we have demonstrated that α 2B-adrenergic receptor (α 2B-AR) interacts with ADP-ribosylation factor 1 (ARF1), a small GTPase involved in vesicle-mediated trafficking, in an agonist activation-dependent manner and that the interaction is mediated through a unique double Trp motif in the third intracellular loop of the receptor. Interestingly, mutation of the double Trp motif and siRNA-mediated depletion of ARF1 attenuate α 2B-AR-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) without altering receptor intracellular trafficking, whereas expression of the constitutively active mutant ARF1Q71L and ARNO, a GDP-GTP exchange factor of ARF1, markedly enhances the activation of Raf1, MEK1, and ERK1/2. These data strongly demonstrate that the small GTPase ARF1 modulates ERK1/2 activation by α 2B-AR and provide the first evidence indicating a novel function for ARF1 in regulating the MAPK signaling pathway.
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U2 - 10.1074/jbc.M111.267286
DO - 10.1074/jbc.M111.267286
M3 - Article
C2 - 22025613
AN - SCOPUS:83355169690
SN - 0021-9258
VL - 286
SP - 43361
EP - 43369
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 50
ER -