PMID- 10347142
OWN - NLM
STAT- MEDLINE
DCOM- 19990701
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 23
DP  - 1999 Jun 4
TI  - Feedback regulation of beta-arrestin1 function by extracellular signal-regulated 
      kinases.
PG  - 15971-4
AB  - The functions of beta-arrestin1 to facilitate clathrin-mediated endocytosis of
      the beta2-adrenergic receptor and to promote agonist-induced activation of
      extracellular signal-regulated kinases (ERK) are regulated by its
      phosphorylation/dephosphorylation at Ser-412. Cytoplasmic beta-arrestin1 is
      almost stoichiometrically phosphorylated at Ser-412. Dephosphorylation of
      beta-arrestin1 at the plasma membrane is required for targeting a signaling
      complex that includes the agonist-occupied receptors to the clathrin-coated pits.
      Here we demonstrate that beta-arrestin1 phosphorylation and function are
      modulated by an ERK-dependent negative feedback mechanism. ERK1 and ERK2
      phosphorylate beta-arrestin1 at Ser-412 in vitro. Inhibition of ERK activity by a
      dominant-negative MEK1 mutant significantly attenuates beta-arrestin1
      phosphorylation, thereby increasing the concentration of dephosphorylated
      beta-arrestin1. Under such conditions, beta-arrestin1-mediated beta2-adrenergic
      receptor internalization is enhanced as is its ability to bind clathrin. In
      contrast, if ERK-mediated phosphorylation is increased by transfection of a
      constitutively active MEK1 mutant, receptor internalization is inhibited. Our
      results suggest that dephosphorylated beta-arrestin1 mediates
      endocytosis-dependent ERK activation. Following activation, ERKs phosphorylate
      beta-arrestin1, thereby exerting an inhibitory feedback control of its function.
FAU - Lin, F T
AU  - Lin FT
AD  - Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke
      University Medical Center, Durham, North Carolina 27710, USA.
FAU - Miller, W E
AU  - Miller WE
FAU - Luttrell, L M
AU  - Luttrell LM
FAU - Lefkowitz, R J
AU  - Lefkowitz RJ
LA  - eng
GR  - HL16037/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Arrestins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (beta-Arrestins)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Arrestins/*physiology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cell Line
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Feedback
MH  - Humans
MH  - MAP Kinase Kinase 1
MH  - *Mitogen-Activated Protein Kinase Kinases
MH  - Peptide Mapping
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/antagonists & inhibitors
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - Serine/metabolism
MH  - beta-Arrestins
EDAT- 1999/05/29 00:00
MHDA- 1999/05/29 00:01
CRDT- 1999/05/29 00:00
PHST- 1999/05/29 00:00 [pubmed]
PHST- 1999/05/29 00:01 [medline]
PHST- 1999/05/29 00:00 [entrez]
AID - 10.1074/jbc.274.23.15971 [doi]
AID - S0021-9258(19)72927-5 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 4;274(23):15971-4. doi: 10.1074/jbc.274.23.15971.