| pubmed-article:17135240 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17135240 | lifeskim:mentions | umls-concept:C0023779 | lld:lifeskim |
| pubmed-article:17135240 | lifeskim:mentions | umls-concept:C0014139 | lld:lifeskim |
| pubmed-article:17135240 | lifeskim:mentions | umls-concept:C0031621 | lld:lifeskim |
| pubmed-article:17135240 | lifeskim:mentions | umls-concept:C0031678 | lld:lifeskim |
| pubmed-article:17135240 | lifeskim:mentions | umls-concept:C0763620 | lld:lifeskim |
| pubmed-article:17135240 | lifeskim:mentions | umls-concept:C1416448 | lld:lifeskim |
| pubmed-article:17135240 | lifeskim:mentions | umls-concept:C1419227 | lld:lifeskim |
| pubmed-article:17135240 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:17135240 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:17135240 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:17135240 | pubmed:dateCreated | 2007-1-22 | lld:pubmed |
| pubmed-article:17135240 | pubmed:abstractText | Endocytosis of Eph receptors is critical for a number of biological processes, including modulating axon growth cone collapse response and regulating cell surface levels of receptor in epithelial cells. In particular, ephrin-A ligand stimulation of tumor cells induces EphA2 receptor internalization and degradation, a process that has been explored as a means to reduce tumor malignancy. However, the mechanism and regulation of ligand-induced Eph receptor internalization are not well understood. Here we show that SHIP2 (Src homology 2 domain-containing phosphoinositide 5-phosphatase 2) is recruited to activated EphA2 via a heterotypic sterile alpha motif (SAM)-SAM domain interaction, leading to regulation of EphA2 internalization. Overexpression of SHIP2 inhibits EphA2 receptor endocytosis, whereas suppression of SHIP2 expression by small interfering RNA-mediated gene silencing promotes ligand-induced EphA2 internalization and degradation. SHIP2 regulates EphA2 endocytosis via phosphatidylinositol 3-kinase-dependent Rac1 activation. Phosphatidylinositol 3,4,5-trisphosphate levels are significantly elevated in SHIP2 knockdown cells, phosphatidylinositol 3-kinase inhibitor decreases phosphatidylinositol 3,4,5-trisphosphate levels and suppresses increased EphA2 endocytosis. Ephrin-A1 stimulation activates Rac1 GTPase, and the Rac1-GTP levels are further increased in SHIP2 knockdown cells. A dominant negative Rac1 GTPase effectively inhibited ephrin-A1-induced EphA2 endocytosis. Together, our findings provide evidence that recruitment of SHIP2 to EphA2 attenuates a positive signal to receptor endocytosis mediated by phosphatidylinositol 3-kinase and Rac1 GTPase. | lld:pubmed |
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| pubmed-article:17135240 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17135240 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17135240 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17135240 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:17135240 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17135240 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:17135240 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17135240 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17135240 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17135240 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17135240 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17135240 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:17135240 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:17135240 | pubmed:author | pubmed-author:DeebZ EZE | lld:pubmed |
| pubmed-article:17135240 | pubmed:author | pubmed-author:ZhuangGuangle... | lld:pubmed |
| pubmed-article:17135240 | pubmed:author | pubmed-author:HwangYoonhaY | lld:pubmed |
| pubmed-article:17135240 | pubmed:author | pubmed-author:HunterSonjaS | lld:pubmed |
| pubmed-article:17135240 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17135240 | pubmed:day | 26 | lld:pubmed |
| pubmed-article:17135240 | pubmed:volume | 282 | lld:pubmed |
| pubmed-article:17135240 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17135240 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17135240 | pubmed:pagination | 2683-94 | lld:pubmed |
| pubmed-article:17135240 | pubmed:dateRevised | 2010-11-18 | lld:pubmed |
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| pubmed-article:17135240 | pubmed:meshHeading | pubmed-meshheading:17135240... | lld:pubmed |
| pubmed-article:17135240 | pubmed:meshHeading | pubmed-meshheading:17135240... | lld:pubmed |
| pubmed-article:17135240 | pubmed:meshHeading | pubmed-meshheading:17135240... | lld:pubmed |
| pubmed-article:17135240 | pubmed:meshHeading | pubmed-meshheading:17135240... | lld:pubmed |
| pubmed-article:17135240 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17135240 | pubmed:articleTitle | Regulation of EphA2 receptor endocytosis by SHIP2 lipid phosphatase via phosphatidylinositol 3-Kinase-dependent Rac1 activation. | lld:pubmed |
| pubmed-article:17135240 | pubmed:affiliation | Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. | lld:pubmed |
| pubmed-article:17135240 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17135240 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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