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Uncoupling of cell proliferation and differentiation activities of basic fibroblast growth factor
Author(s) -
Bailly Karine,
Soulet Fabienne,
Leroy Didier,
Amalric Francois,
Bouche Gerard
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.14.2.333
Subject(s) - fibroblast growth factor , microbiology and biotechnology , cell growth , phosphorylation , biology , mutant , signal transduction , casein kinase 2 , receptor , chemistry , protein kinase a , biochemistry , mitogen activated protein kinase kinase , gene
FGF‐2 exerts its pleiotropic effects on cell growth and differentiation by interacting with specific cell surface receptors. In addition, exogenously added FGF‐2 is translocated from outside the cell to the nucleus during G1‐S transition. In this study, we show that a single point mutation in FGF‐2 (substitution of residue serine 117 by alanine) is sufficient to drastically reduce its mitogenic activity without affecting its differentiation properties. The FGF‐2(S117A) mutant binds to and activates tyrosine kinase receptors and induces MAPK and p70S6K activation as strongly as the wild‐type FGF‐2. We demonstrate that this mutant enters NIH3T3 cells, is translocated to the nucleus, and is phosphorylated similar to the wild‐type growth factor. This suggests that FGF‐2 mitogenic activity may require, in addition to signaling through cell surface receptors and nuclear translocation, activation of nuclear targets. We have previously shown that, in vitro , FGF‐2 directly stimulates the activity of the casein kinase 2 (CK2), a ubiquitous serine/threonine kinase involved in the control of cell proliferation. We report that, in vivo , FGF‐2(WT) transiently interacts with CK2 and stimulates its activity in the nucleus during G1‐S transition in NIH3T3 cells. In contrast, the FGF‐2(S117A) mutant fails to interact with CK2. Thus, our results show that FGF‐2 mitogenic and differentiation activities can be dissociated by a single point mutation and that CK2 may be a new nuclear effector involved in FGF‐2 mitogenic activity. Bailly, K., Soulet, F., Leroy, D., Amalric, F., Bouche, G. Uncoupling of cell proliferation and differentiation activities of basic fibroblast growth factor (FGF‐2). FASEB J. 14, 333—344 (2000)