Linked Life Data

11013230

Source:http://linkedlifedata.com/resource/pubmed/id/11013230

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2001-1-18
pubmed:abstractText
Both beta(2)- and beta(3)-adrenergic receptors (ARs) are able to activate the extracellular signal-regulated kinase (ERK) pathway. We previously showed that c-Src is required for ERK activation by beta(2)AR and that it is recruited to activated beta(2)AR through binding of the Src homology 3 (SH3) domain to proline-rich regions of the adapter protein beta-arrestin1. Despite the absence of sites for phosphorylation and beta-arrestin binding, ERK activation by beta(3)AR still requires c-Src. Agonist activation of beta(2)AR, but not beta(3)AR, led to redistribution of green fluorescent protein-tagged beta-arrestin to the plasma membrane. In beta-arrestin-deficient COS-7 cells, beta-agonist-dependent co-precipitation of c-Src with the beta(2)AR required exogenous beta-arrestin, but activated beta(3)AR co-precipitated c-Src in the absence or presence of beta-arrestin. ERK activation and Src co-precipitation with beta(3)AR also occurred in adipocytes in an agonist-dependent and pertussis toxin-sensitive manner. Protein interaction studies show that the beta(3)AR interacts directly with the SH3 domain of Src through proline-rich motifs (PXXP) in the third intracellular loop and the carboxyl terminus. ERK activation and Src co-precipitation were abolished in cells expressing point mutations in these PXXP motifs. Together, these data describe a novel mechanism of ERK activation by a G protein-coupled receptor in which the intracellular domains directly recruit c-Src.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38131-4
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11013230-Adipocytes, pubmed-meshheading:11013230-Adrenergic beta-Agonists, pubmed-meshheading:11013230-Amino Acid Sequence, pubmed-meshheading:11013230-Animals, pubmed-meshheading:11013230-Arrestins, pubmed-meshheading:11013230-Binding Sites, pubmed-meshheading:11013230-COS Cells, pubmed-meshheading:11013230-Cell Differentiation, pubmed-meshheading:11013230-Cell Line, pubmed-meshheading:11013230-Cercopithecus aethiops, pubmed-meshheading:11013230-Dioxoles, pubmed-meshheading:11013230-Enzyme Activation, pubmed-meshheading:11013230-Isoproterenol, pubmed-meshheading:11013230-Mice, pubmed-meshheading:11013230-Mitogen-Activated Protein Kinases, pubmed-meshheading:11013230-Molecular Sequence Data, pubmed-meshheading:11013230-Proline, pubmed-meshheading:11013230-Propranolol, pubmed-meshheading:11013230-Proto-Oncogene Proteins pp60(c-src), pubmed-meshheading:11013230-Receptors, Adrenergic, beta-3, pubmed-meshheading:11013230-Transfection
pubmed:year
2000
pubmed:articleTitle
Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation.
pubmed:affiliation
Departments of Psychiatry and Behavioral Sciences, Pharmacology, and Medicine and the Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
pubmed:publicationType
Journal Article