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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Kanda, Shigeru Hodgkin, Matthew N. Woodfield, Richard J. Wakelam, Michael J. O. Thomas, George Claesson-Welsh, Lena |
| Abstract | p70s6k has a role in cell cycle progression in response to specific extracellular stimuli. The signal transduction pathway leading to activation of p70s6k by fibroblast growth factor receptor-1 (FGFR-1) was examined in FGF-2-treated rat L6 myoblasts. p70s6k was activated in a biphasic and rapamycin-sensitive manner. Although phosphatidylinositol 3′-kinase was not activated in the FGF-2 treated cells, as judged fromin vitro and in vivo analyses, wortmannin and LY294002 treatment inhibited p70s6k activation. Inhibition of protein kinase C (PKC), by bisindolylmaleimide or by chronic phorbol ester treatment of the FGFR-1 cells, suppressed but did not block p70s6k activation. In cells expressing a point-mutated FGFR-1, Y766F, unable to mediate PKC activation, p70s6k was still activated, in a bisindolylmaleimide- and phorbol ester-resistant manner. The involvement of S6 kinase in FGFR-1-dependent biological responses was examined in murine brain endothelial cells. In response to FGF-2, these cells differentiate to form tube-like structures in collagen gel cultures and proliferate when cultured on fibronectin. p70s6k was not activated in endothelial cells on collagen, whereas activation was observed during proliferation on fibronectin. In agreement with this finding, rapamycin inhibited the proliferative but not the differentiation response. Our results indicate that FGFR-1 mediates p70s6k activation by a phosphatidylinositol 3′-kinase-independent mechanism that does not require PKC activation and, furthermore, proliferation, but not differentiation of endothelial cells in response to FGF-2, is associated with p70s6k activation. |
| Related Links | http://www.jbc.org/content/272/37/23347.abstract |
| Ending Page | 23353 |
| Starting Page | 23347 |
| Page Count | 7 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 37 |
| Volume Number | 272 |
| DOI | 10.1074/jbc.272.37.23347 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 1997-09-12 |
| Access Restriction | Open |
| Subject Keyword | CELL BIOLOGY AND METABOLISM |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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