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Title
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-arrestin-dependent formation of adrenergic receptor Src protein kinase complexes
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Author
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Abstract
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| The Pas-dependent activation of mitogen-activated protein (MAP) kinase pathways by many receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) requires the activation of Src family tyrosine kinases. Stimulation of beta(2) adrenergic receptors resulted in the assembly of a protein complex containing activated c-Src and the receptor. Src recruitment was mediated by beta-arrestin, which functions as an adapter protein, binding both c-Src and the agonist-occupied receptor. beta-Arrestin 1 mutants, impaired either in c-Src binding or in the ability to target receptors to clathrin-coated pits, acted as dominant negative inhibitors of beta(2) adrenergic receptor-mediated activation of the MAP kinases Erk1 and Erk2. These data suggest that beta-arrestin binding, which terminates receptor-C protein;coupling, also initiates a second wave of signal transduction in which the "desensitized" receptor functions as a critical structural component of a mitogenic signaling complex. |
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Language
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English
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Source (journal)
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Science / American Association for the Advancement of Science [Washington, D.C.] - Washington, D.C., 1880, currens
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Publication
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Washington, D.C.
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American Association for the Advancement of Science
,
1999
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ISSN
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0036-8075
[print]
1095-9203
[online]
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DOI
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10.1126/SCIENCE.283.5402.655
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Volume/pages
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283
:5402
(1999)
, p. 655-661
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ISI
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000078324400032
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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