Source:http://linkedlifedata.com/resource/pubmed/id/17335807
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2007-3-23
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| pubmed:abstractText |
Cancer cells depend on chemotaxis for invasion and frequently overexpress and/or activate Src. We previously reported that v-Src accelerates motility by promoting phosphoinositide 3-kinase (PI3-K) signalling but abrogates chemotaxis. We here addressed the mechanism of the loss of chemotactic response to platelet-derived growth factor (PDGF) gradients in fibroblasts harbouring a thermosensitive v-Src kinase. At non-permissive temperature, PDGF receptor (PDGFR) signalling, assessed by phosphoY(751)-specific antibodies (a docking site for PI3-K), was not detected without PDGF and showed a concentration-dependent PDGF response. Both immunolabeling of PI3-K (p110) and live cell imaging of its product (phosphatidylinositol 3,4,5 tris-phosphate) showed PI3-K recruitment and activation at lamellipodia polarized towards a PDGF gradient. Centrosomes and PDGFR- and Src-bearing endosomes were also oriented towards this gradient. Upon v-Src thermoactivation, (i) Y(751) phosphorylation was moderately induced without PDGF and synergistically increased with PDGF; (ii) PI3-K was recruited and activated all along the plasma membrane without PDGF and did not polarize in response to a PDGF gradient; and (iii) polarization of centrosomes and of PDGFR-bearing endosomes were also abrogated. Thus, PDGF can further increase PDGFR auto-phosphorylation despite strong Src kinase activity, but diffuse downstream activation of PI3-K by Src abrogates cell polarization and chemotaxis: "signalling requires silence".
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein pp60(v-src),
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Platelet-Derived Growth...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0014-4827
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
313
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1090-105
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:17335807-Animals,
pubmed-meshheading:17335807-Cell Line,
pubmed-meshheading:17335807-Cell Membrane,
pubmed-meshheading:17335807-Centrosome,
pubmed-meshheading:17335807-Chemotaxis,
pubmed-meshheading:17335807-Cytoplasm,
pubmed-meshheading:17335807-Cytoskeleton,
pubmed-meshheading:17335807-Enzyme Activation,
pubmed-meshheading:17335807-Fibroblasts,
pubmed-meshheading:17335807-Focal Adhesions,
pubmed-meshheading:17335807-Microtubule-Organizing Center,
pubmed-meshheading:17335807-Oncogene Protein pp60(v-src),
pubmed-meshheading:17335807-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17335807-Platelet-Derived Growth Factor,
pubmed-meshheading:17335807-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:17335807-Rats,
pubmed-meshheading:17335807-Receptors, Platelet-Derived Growth Factor,
pubmed-meshheading:17335807-Signal Transduction
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| pubmed:year |
2007
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| pubmed:articleTitle |
Constitutive diffuse activation of phosphoinositide 3-kinase at the plasma membrane by v-Src suppresses the chemotactic response to PDGF by abrogating the polarity of PDGF receptor signalling.
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| pubmed:affiliation |
Université catholique de Louvain, Christian de Duve Institute of Cellular Pathology, CELL Unit, UCL 75.41, avenue Hippocrate, 75, B-1200 Brussels, Belgium.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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