PMID- 23527545
OWN - NLM
STAT- MEDLINE
DCOM- 20130806
LR  - 20211021
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 452
IP  - 3
DP  - 2013 Jun 15
TI  - The Arf GAP AGAP2 interacts with beta-arrestin2 and regulates beta2-adrenergic receptor 
      recycling and ERK activation.
PG  - 411-21
LID - 10.1042/BJ20121004 [doi]
AB  - AGAP2 [Arf (ADP-ribosylation factor) GAP (GTPase-activating protein) with 
      GTP-binding-protein-like, ankyrin repeat and PH (pleckstrin homology) domains] is 
      a multidomain Arf GAP that was shown to promote the fast recycling of transferrin 
      receptors. In the present study we tested the hypothesis that AGAP2 regulates the 
      trafficking of beta2-adrenergic receptors. We found that AGAP2 formed a complex with 
      beta-arrestin1 and beta-arrestin2, proteins that are known to regulate beta2-adrenergic 
      receptor signalling and trafficking. AGAP2 co-localized with beta-arrestin2 on the 
      plasma membrane, and knockdown of AGAP2 expression reduced plasma membrane 
      association of beta-arrestin2 upon beta2-adrenergic receptor activation. AGAP2 also 
      co-localized with internalized beta2-adrenergic receptors on endosomes, and 
      overexpression of AGAP2 slowed accumulation of beta2-adrenergic receptor in the 
      perinuclear recycling endosomes. In contrast, knockdown of AGAP2 expression 
      prevented the recycling of the beta2-adrenergic receptor back to the plasma 
      membrane. In addition, AGAP2 formed a complex with endogenous ERK 
      (extracellular-signal-regulated kinase) and overexpression of AGAP2 potentiated 
      ERK phosphorylation induced by beta2-adrenergic receptors. Taken together, these 
      results support the hypothesis that AGAP2 plays a role in the signalling and 
      recycling of beta2-adrenergic receptors.
FAU - Wu, Yuanjun
AU  - Wu Y
AD  - Department of Urology and Prostate Disease Center, University of Florida College 
      of Medicine, Gainesville, FL 32610, USA.
FAU - Zhao, Yu
AU  - Zhao Y
FAU - Ma, Xiaojie
AU  - Ma X
FAU - Zhu, Yunjuan
AU  - Zhu Y
FAU - Patel, Jaimin
AU  - Patel J
FAU - Nie, Zhongzhen
AU  - Nie Z
LA  - eng
GR  - K22 CA124578/CA/NCI NIH HHS/United States
GR  - K22CA124578/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Arrestins)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0 (beta-Arrestins)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.6.1.- (AGAP2 protein, human)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Arrestins/*metabolism
MH  - Cell Line, Tumor
MH  - Enzyme Activation/genetics
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - GTP-Binding Proteins/antagonists & inhibitors/*metabolism/physiology
MH  - GTPase-Activating Proteins/antagonists & inhibitors/*metabolism/physiology
MH  - Gene Knockdown Techniques
MH  - HEK293 Cells
MH  - Humans
MH  - Protein Binding/genetics
MH  - Protein Transport/genetics
MH  - Receptors, Adrenergic, beta-2/biosynthesis/genetics/*metabolism
MH  - Signal Transduction/genetics
MH  - beta-Arrestins
PMC - PMC3952494
MID - NIHMS514886
EDAT- 2013/03/27 06:00
MHDA- 2013/08/07 06:00
PMCR- 2014/03/13
CRDT- 2013/03/27 06:00
PHST- 2013/03/27 06:00 [entrez]
PHST- 2013/03/27 06:00 [pubmed]
PHST- 2013/08/07 06:00 [medline]
PHST- 2014/03/13 00:00 [pmc-release]
AID - BJ20121004 [pii]
AID - 10.1042/BJ20121004 [doi]
PST - ppublish
SO  - Biochem J. 2013 Jun 15;452(3):411-21. doi: 10.1042/BJ20121004.