FGF-1-Dependent Proliferative and Migratory Responses Are Impaired in Senescent Human Umbilical Vein Endothelial Cells and Correlate with the Inability to Signal Tyrosine Phosphorylation of Fibroblast Growth Factor Receptor-1 Substrates
Senescent cells do not proliferate in response to exogenous growth factors, yet the number and affinity of growth factor receptors on the cell surface appear to be similar to presenescent cell populations. To determine whether a defect in receptor signaling exists, we analyzed human umbilical vein e...
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Published in | The Journal of cell biology Vol. 134; no. 3; pp. 783 - 791 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Rockefeller University Press
01.08.1996
The Rockefeller University Press |
Subjects | |
Online Access | Get full text |
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Summary: | Senescent cells do not proliferate in response to exogenous growth factors, yet the number and affinity of growth factor receptors on the cell surface appear to be similar to presenescent cell populations. To determine whether a defect in receptor signaling exists, we analyzed human umbilical vein endothelial cells (HUVEC) since HUVEC growth is absolutely dependent upon the presence of FGF. We report that in both presenescent and senescent HUVEC populations, FGF-1 induces the expression of cell cycle-specific genes, suggesting that functional FGF receptor (FGFR) may exist on the surface of these cells. However, the tyrosine phosphorylation of FGFR-1 substrates, Src and cortactin, is impaired in senescent HUVEC, and only the presenescent cell populations exhibit a FGF-1-dependent Src tyrosine kinase activity. Moreover, we demonstrate that senescent HUVEC are unable to migrate in response to FGF-1, and these data correlate with an altered organization of focal adhesion sites. These data suggest that the induction of gene expression is insufficient to promote a proliferative or migratory phenotype in senescent HUVEC and that the attenuation of the FGFR-1 signal transduction pathway may be involved in the inability of senescent HUVEC to proliferate and/or migrate. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9525 1540-8140 |
DOI: | 10.1083/jcb.134.3.783 |