S100B protein regulates myoblast proliferation and differentiation by activating FGFR1 in a bFGF-dependent manner.
S100B protein has been shown to exert anti-myogenic and mitogenic effects in myoblast cultures through inhibition of the myogenic p38 MAPK and activation of the mitogenic ERK1/2. However, the receptor mediating these effects had not been identified. Here, we show that S100B increases and/or stabilizes the binding of basic fibroblast ... growth factor (bFGF) to bFGF receptor 1 (FGFR1) by interacting with bFGF, thereby enhancing FGFR1 activation and the mitogenic and anti-myogenic effects of FGFR1. S100B also binds to its canonical receptor RAGE (receptor for advanced glycation end-products), a multi-ligand receptor previously shown to transduce a pro-myogenic signal when activated by HMGB1, and recruits RAGE into a RAGE-S100B-bFGF-FGFR1 complex. However, when bound to S100B-bFGF-FGFR1, RAGE can no longer stimulate myogenic differentiation, whereas in the absence of either bFGF or FGFR1, binding of S100B to RAGE results in stimulation of RAGE anti-mitogenic and promyogenic signaling. An S100B-bFGF-FGFR1 complex also forms in Rage(-/-) myoblasts, leading to enhanced proliferation and reduced differentiation, which points to a dispensability of RAGE for the inhibitory effects of S100B on myoblasts under the present experimental conditions. These results reveal a new S100B-interacting protein - bFGF - in the extracellular milieu and suggest that S100B stimulates myoblast proliferation and inhibits myogenic differentiation by activating FGFR1 in a bFGF-dependent manner.
Mesh Terms:
Animals, Cell Differentiation, Cell Growth Processes, Cell Line, Fibroblast Growth Factor 2, Humans, Mice, Mice, Inbred C57BL, Myoblasts, Nerve Growth Factors, Phosphorylation, Receptor for Advanced Glycation End Products, Receptor, Fibroblast Growth Factor, Type 1, Receptors, Immunologic, S100 Calcium Binding Protein beta Subunit, S100 Proteins, Signal Transduction, Up-Regulation
Animals, Cell Differentiation, Cell Growth Processes, Cell Line, Fibroblast Growth Factor 2, Humans, Mice, Mice, Inbred C57BL, Myoblasts, Nerve Growth Factors, Phosphorylation, Receptor for Advanced Glycation End Products, Receptor, Fibroblast Growth Factor, Type 1, Receptors, Immunologic, S100 Calcium Binding Protein beta Subunit, S100 Proteins, Signal Transduction, Up-Regulation
J. Cell. Sci.
Date: Jul. 15, 2011
PubMed ID: 21693575
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