Publikationsdatum:
2000-11-25
Beschreibung:
beta-Arrestins, originally discovered in the context of heterotrimeric guanine nucleotide binding protein-coupled receptor (GPCR) desensitization, also function in internalization and signaling of these receptors. We identified c-Jun amino-terminal kinase 3 (JNK3) as a binding partner of beta-arrestin 2 using a yeast two-hybrid screen and by coimmunoprecipitation from mouse brain extracts or cotransfected COS-7 cells. The upstream JNK activators apoptosis signal-regulating kinase 1 (ASK1) and mitogen-activated protein kinase (MAPK) kinase 4 were also found in complex with beta-arrestin 2. Cellular transfection of beta-arrestin 2 caused cytosolic retention of JNK3 and enhanced JNK3 phosphorylation stimulated by ASK1. Moreover, stimulation of the angiotensin II type 1A receptor activated JNK3 and triggered the colocalization of beta-arrestin 2 and active JNK3 to intracellular vesicles. Thus, beta-arrestin 2 acts as a scaffold protein, which brings the spatial distribution and activity of this MAPK module under the control of a GPCR.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDonald, P H -- Chow, C W -- Miller, W E -- Laporte, S A -- Field, M E -- Lin, F T -- Davis, R J -- Lefkowitz, R J -- CA65861/CA/NCI NIH HHS/ -- CA85422/CA/NCI NIH HHS/ -- HL16037/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2000 Nov 24;290(5496):1574-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Box 3821, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11090355" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Angiotensin II/metabolism/pharmacology
;
Animals
;
Arrestins/genetics/*metabolism
;
COS Cells
;
Cell Line
;
Cell Nucleus/metabolism
;
Cytosol/enzymology/metabolism
;
Endosomes/enzymology/metabolism
;
Enzyme Activation
;
Humans
;
*MAP Kinase Kinase 4
;
MAP Kinase Kinase Kinase 5
;
MAP Kinase Kinase Kinases/*metabolism
;
*MAP Kinase Signaling System
;
Mice
;
Mitogen-Activated Protein Kinase 10
;
Mitogen-Activated Protein Kinase Kinases/metabolism
;
Mitogen-Activated Protein Kinases/*metabolism
;
Mutation
;
Phosphorylation
;
Protein-Tyrosine Kinases/*metabolism
;
Proto-Oncogene Proteins c-jun/metabolism
;
Rats
;
Receptor, Angiotensin, Type 1
;
Receptors, Angiotensin/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Transfection
;
Two-Hybrid System Techniques
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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