|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0164786,
umls-concept:C0248266,
umls-concept:C0812228,
umls-concept:C1335280,
umls-concept:C1514562,
umls-concept:C1514873,
umls-concept:C1519249,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1704259,
umls-concept:C1704675,
umls-concept:C1705987,
umls-concept:C1706044,
umls-concept:C1879547
|
|
pubmed:issue |
10
|
|
pubmed:dateCreated |
2006-10-3
|
|
pubmed:abstractText |
SHP-2 is a tyrosine phosphatase which functions as a positive regulator downstream of RTKs, activating growth-stimulatory signalling pathways. To date, very few G protein-coupled receptors (GPCRs) have been shown to be connected to SHP-2 and very little is known about the positive role of SHP-2 in GPCR signalling. The CCK2 receptor (CCK2R), a GPCR, is now recognized to mediate mitogenic effects of gastrin on gastrointestinal cells. In the present study, we demonstrate the role of SHP-2 in the activation of the AKT pathway by the CCK2R in COS-7 cells transfected with the CCK2R and in a pancreatic cancer cell line expressing the endogenous receptor. Using surface plasmon resonance analysis, we identified a highly conserved ITIM motif, containing the tyrosine residue 438, located in the C-terminal intracellular tail of the CCK2R which directly interacts with the SHP-2 SH2 domains. The interaction was confirmed by pull down assays and co-immunoprecipitation of the receptor with SHP-2. This interaction was transiently increased following gastrin stimulation of the CCK2R and correlated with the tyrosine phosphorylation of SHP-2. Mutational analysis of the key ITIM residue 438 confirmed that the CCK2R ITIM sequence is required for interaction with SHP-2 and the activation of the AKT pathway.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Gastrins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Cholecystokinin B,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
0006-3002
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
1763
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1098-107
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:16963136-Amino Acid Motifs,
pubmed-meshheading:16963136-Amino Acid Sequence,
pubmed-meshheading:16963136-Animals,
pubmed-meshheading:16963136-COS Cells,
pubmed-meshheading:16963136-Cell Line, Tumor,
pubmed-meshheading:16963136-Cercopithecus aethiops,
pubmed-meshheading:16963136-Gastrins,
pubmed-meshheading:16963136-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16963136-Mice,
pubmed-meshheading:16963136-Molecular Sequence Data,
pubmed-meshheading:16963136-NIH 3T3 Cells,
pubmed-meshheading:16963136-Pancreatic Neoplasms,
pubmed-meshheading:16963136-Phosphorylation,
pubmed-meshheading:16963136-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:16963136-Protein Tyrosine Phosphatases,
pubmed-meshheading:16963136-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16963136-Rats,
pubmed-meshheading:16963136-Receptor, Cholecystokinin B,
pubmed-meshheading:16963136-Signal Transduction,
pubmed-meshheading:16963136-Tyrosine
|
|
pubmed:year |
2006
|
|
pubmed:articleTitle |
An ITIM-like motif within the CCK2 receptor sequence required for interaction with SHP-2 and the activation of the AKT pathway.
|
|
pubmed:affiliation |
INSERM U 531, IFR 31, Institut Louis Bugnard, BP 84225, 31432 Toulouse cedex 4, France.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
