PI3-kinase activation by GM-CSF in endothelium is upstream of Jak/Stat pathway: Role of αGMR Journal Article
| Authors: | Dhar Mascareno, M.; Pedraza, A.; Golde, D. W. |
| Article Title: | PI3-kinase activation by GM-CSF in endothelium is upstream of Jak/Stat pathway: Role of αGMR |
| Abstract: | GM-CSF has been identified as a growth factor for endothelial cells. In this study, we investigated the role of PI3-kinase pathway in mediating GM-CSF induced angiogenesis. GM-CSF induced tube formation in human umbilical vein endothelial cells, as examined using Matrigel assay, was inhibited by specific inhibitors of PI3-kinase, wortmannin, and LY294002. The regulatory subunit of PI3-kinase (p85) interacted with αGMR via its C-SH2 domain in a GM-CSF-dependent fashion with concomitant phosphorylation of p85 and activation of PI3-kinase pathway. p85 binding site on the αGMR was essential to induce GM-CSF receptor-dependent Stat activation. Furthermore, inhibition of PI3-kinase activity also abrogated GM-CSF induced Stat activation. These studies underscore the significance of the GM-CSF mediated PI3-kinase activation and its role in angiogenesis. © 2005 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; human cell; dna-binding proteins; cells, cultured; enzyme inhibition; granulocyte macrophage colony stimulating factor; enzyme activation; angiogenesis; phosphorylation; phosphatidylinositol 3 kinase; endothelial cells; umbilical vein; umbilical veins; enzyme inhibitors; janus kinase; 1-phosphatidylinositol 3-kinase; binding site; binding sites; protein-tyrosine kinases; trans-activators; matrigel; endothelium; 2 morpholino 8 phenylchromone; wortmannin; stat protein; gm-csf; granulocyte-macrophage colony-stimulating factor; protein p85; stat transcription factors; pi3-kinase; granulocyte macrophage colony stimulating factor receptor; receptors, granulocyte-macrophage colony-stimulating factor; αgmr; angiogenesis inducing agents |
| Journal Title: | Biochemical and Biophysical Research Communications |
| Volume: | 337 |
| Issue: | 2 |
| ISSN: | 0006-291X |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2005-11-18 |
| Start Page: | 551 |
| End Page: | 556 |
| Language: | English |
| DOI: | 10.1016/j.bbrc.2005.09.088 |
| PUBMED: | 16202975 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 24 October 2012" - "CODEN: BBRCA" - "Source: Scopus" |
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