The beta1-adrenergic receptor mediates extracellular signal-regulated kinase activation via Galphas.
beta-Adrenergic receptors can activate extracellular signal-regulated kinases (ERKs) via different mechanisms. In this study, we investigated the molecular mechanism of beta1-adrenergic receptor (beta1AR)-mediated ERK activation in African green monkey kidney COS-7 cells. Treatment of cells with isoproterenol (ISO), a beta1AR selective agonist, induced phosphorylation of ERK1/2 in a dose-dependent manner. ISO-stimulated ERK phosphorylation was not influenced by the Gbetagamma inhibitor, betaAR kinase carboxyl terminal (betaARKct) or by the Gi inhibitor, pertussis toxin (PTX), but it was clearly abolished via inhibition of protein kinase A (PKA) with H89, or of mitogen-activated protein kinase kinase (MEK1) with PD98059, revealing that the Galphas subunit is involved in ERK regulation through the PKA/MEK1 pathway. We also tested the effect of the adenylate cyclase activator forskolin on ERK activation, and the result was identical to that of ISO stimulation. Moreover, pretreatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 or with the Src tyrosine kinase inhibitor PP2 did not affect ERK activation. These observations suggest a mechanism of beta1AR-mediated ERK activity that involves the Galphas subunit, but not EGFR or Src tyrosine kinase.
Zheng
Junfang
J
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, People's Republic of China.
Shen
Hui
H
Xiong
Ying
Y
Yang
Xiaomei
X
He
Junqi
J
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D011943:Receptors, Adrenergic, beta; D048049:Extracellular Signal-Regulated MAP Kinases; D019205:GTP-Binding Protein alpha Subunits, Gs