|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
9
|
|
pubmed:dateCreated |
2004-2-23
|
|
pubmed:abstractText |
Many G protein-coupled receptors activate growth factor receptors, although the mechanisms controlling this transactivation are unclear. We have identified two proline-rich, SH3 binding sites (PXXP) in the carboxyl-terminal tail of the human P2Y(2) nucleotide receptor that directly associate with the tyrosine kinase Src in protein binding assays. Furthermore, Src co-precipitated with the P2Y(2) receptor in 1321N1 astrocytoma cells stimulated with the P2Y(2) receptor agonist UTP. A mutant P2Y(2) receptor lacking the PXXP motifs was found to stimulate calcium mobilization and serine/threonine phosphorylation of the Erk1/2 mitogen-activated protein kinases, like the wild-type receptor, but was defective in its ability to stimulate tyrosine phosphorylation of Src and Src-dependent tyrosine phosphorylation of the proline-rich tyrosine kinase 2, epidermal growth factor receptor (EGFR), and platelet-derived growth factor receptor. Dual immunofluorescence labeling of the P2Y(2) receptor and the EGFR indicated that UTP caused an increase in the co-localization of these receptors in the plasma membrane that was prevented by the Src inhibitor PP2. Together, these data suggest that agonist-induced binding of Src to the SH3 binding sites in the P2Y(2) receptor facilitates Src activation, which recruits the EGFR into a protein complex with the P2Y(2) receptor and allows Src to efficiently phosphorylate the EGFR.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AG 1879,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/P2RY2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/P2ry2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptk2b protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2Y2,
http://linkedlifedata.com/resource/pubmed/chemical/Uridine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
27
|
|
pubmed:volume |
279
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
8212-8
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:14670955-Amino Acid Sequence,
pubmed-meshheading:14670955-Animals,
pubmed-meshheading:14670955-Astrocytoma,
pubmed-meshheading:14670955-Binding Sites,
pubmed-meshheading:14670955-Calcium,
pubmed-meshheading:14670955-Cell Membrane,
pubmed-meshheading:14670955-Fluorescent Antibody Technique,
pubmed-meshheading:14670955-Focal Adhesion Kinase 2,
pubmed-meshheading:14670955-Humans,
pubmed-meshheading:14670955-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:14670955-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:14670955-Mitogen-Activated Protein Kinases,
pubmed-meshheading:14670955-Molecular Sequence Data,
pubmed-meshheading:14670955-Mutagenesis,
pubmed-meshheading:14670955-PC12 Cells,
pubmed-meshheading:14670955-Peptide Fragments,
pubmed-meshheading:14670955-Phosphorylation,
pubmed-meshheading:14670955-Protein-Tyrosine Kinases,
pubmed-meshheading:14670955-Pyrimidines,
pubmed-meshheading:14670955-Rats,
pubmed-meshheading:14670955-Receptor, Epidermal Growth Factor,
pubmed-meshheading:14670955-Receptors, Platelet-Derived Growth Factor,
pubmed-meshheading:14670955-Receptors, Purinergic P2,
pubmed-meshheading:14670955-Receptors, Purinergic P2Y2,
pubmed-meshheading:14670955-Transfection,
pubmed-meshheading:14670955-Tumor Cells, Cultured,
pubmed-meshheading:14670955-Uridine Triphosphate,
pubmed-meshheading:14670955-src Homology Domains,
pubmed-meshheading:14670955-src-Family Kinases
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Src homology 3 binding sites in the P2Y2 nucleotide receptor interact with Src and regulate activities of Src, proline-rich tyrosine kinase 2, and growth factor receptors.
|
|
pubmed:affiliation |
Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65212, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
