PMID- 19037712
OWN - NLM
STAT- MEDLINE
DCOM- 20100402
LR  - 20191210
IS  - 1438-2199 (Electronic)
IS  - 0939-4451 (Linking)
VI  - 38
IP  - 1
DP  - 2010 Jan
TI  - The beta1-adrenergic receptor mediates extracellular signal-regulated kinase 
      activation via Galphas.
PG  - 75-84
LID - 10.1007/s00726-008-0207-6 [doi]
AB  - 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.
FAU - Zheng, Junfang
AU  - Zheng J
AD  - Department of Biochemistry and Molecular Biology, Capital Medical University, 
      Beijing, People's Republic of China.
FAU - Shen, Hui
AU  - Shen H
FAU - Xiong, Ying
AU  - Xiong Y
FAU - Yang, Xiaomei
AU  - Yang X
FAU - He, Junqi
AU  - He J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081127
PL  - Austria
TA  - Amino Acids
JT  - Amino acids
JID - 9200312
RN  - 0 (Receptors, Adrenergic, beta)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/*metabolism
MH  - GTP-Binding Protein alpha Subunits, Gs/genetics/*metabolism
MH  - Humans
MH  - Phosphorylation
MH  - Receptors, Adrenergic, beta/genetics/*metabolism
MH  - Signal Transduction
EDAT- 2008/11/28 09:00
MHDA- 2010/04/03 06:00
CRDT- 2008/11/28 09:00
PHST- 2008/07/30 00:00 [received]
PHST- 2008/11/03 00:00 [accepted]
PHST- 2008/11/28 09:00 [pubmed]
PHST- 2010/04/03 06:00 [medline]
PHST- 2008/11/28 09:00 [entrez]
AID - 10.1007/s00726-008-0207-6 [doi]
PST - ppublish
SO  - Amino Acids. 2010 Jan;38(1):75-84. doi: 10.1007/s00726-008-0207-6. Epub 2008 Nov 
      27.