Linked Life Data

18938240

Source:http://linkedlifedata.com/resource/pubmed/id/18938240

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-12-2
pubmed:abstractText
Clathrin-mediated endocytosis is a complex process regulated at many different levels. We showed previously that activation of the angiotensin type 1 receptor (AT1R), which belongs to the G protein-coupled receptor (GPCR) family, leads to c-Src-dependent tyrosine phosphorylation of beta2-adaptin, a subunit of the clathrin adaptor AP-2. The phosphorylation of beta2-adaptin on tyrosine residue 737 (Y737) negatively regulates its interaction with betaarrestin, another important clathrin adaptor for GPCR internalization. Here we sought to determine whether AP-2 phosphorylation represents a general mechanism for different receptors internalizing through the clathrin pathway. Using a specifically designed antibody against the phosphorylated form of Y737 on beta2-adaptin, we demonstrate that this residue is phosphorylated by AT1R in different cell types like HEK293, COS-7 and vascular smooth muscle cells. Using RNA interference approaches, we reveal that this agonist-mediated event is both betaarrestin- and c-Src-dependent, and that it occurs at the plasma membrane in clathrin-coated vesicles (CCVs). We further show that this is not only a common event employed by other GPCRs like the beta2-adrenergic, vasopressin V2, bradykinin type 2, platelet-activating factor and endothelin A receptors but that the epidermal growth factor receptor is capable of eliciting the phosphorylation of AP-2 in CCVs. Our results imply that tyrosine phosphorylation of Y737 on beta2-adaptin is a common regulatory mechanism employed by different receptors undergoing clathrin-dependent endocytosis, and suggest a wider function for this event than originally anticipated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1873-3913
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
103-10
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:18938240-Adaptor Protein Complex 2, pubmed-meshheading:18938240-Adaptor Protein Complex beta Subunits, pubmed-meshheading:18938240-Amino Acid Sequence, pubmed-meshheading:18938240-Angiotensin II, pubmed-meshheading:18938240-Animals, pubmed-meshheading:18938240-Arrestins, pubmed-meshheading:18938240-COS Cells, pubmed-meshheading:18938240-Cell Line, pubmed-meshheading:18938240-Cercopithecus aethiops, pubmed-meshheading:18938240-Clathrin, pubmed-meshheading:18938240-Clathrin-Coated Vesicles, pubmed-meshheading:18938240-Endocytosis, pubmed-meshheading:18938240-Fluorescent Antibody Technique, Direct, pubmed-meshheading:18938240-Gene Knockdown Techniques, pubmed-meshheading:18938240-Humans, pubmed-meshheading:18938240-Phosphorylation, pubmed-meshheading:18938240-Protein-Tyrosine Kinases, pubmed-meshheading:18938240-Receptor, Angiotensin, Type 1, pubmed-meshheading:18938240-Receptor, Epidermal Growth Factor, pubmed-meshheading:18938240-Receptors, G-Protein-Coupled
pubmed:year
2009
pubmed:articleTitle
c-Src-mediated phosphorylation of AP-2 reveals a general mechanism for receptors internalizing through the clathrin pathway.
pubmed:affiliation
Hormones and Cancer Research Unit, Department of Medicine, McGill University Health Center Research Institute, Royal Victoria Hospital, 687 Pine Avenue West, Montréal, Quebec, Canada H3A 1A1.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't