BFGF AND LIF SIGNALING ACTIVATES STAT3 IN PROLIFERATING MYOBLASTS

Different mitogens elicit similar effects on growth and differentiatio n of skeletal muscle, suggesting that potential overlap exists in the signaling cascades activated by such factors. To investigate this poss ibility, we examined the status of STAT and ERK proteins in C2C12 myob lasts and myotubes following stimulation with bFGF or LIF. Both STAT1 and STAT3 as well as ERK1 and ERK2 proteins were detectable in extract s of myoblasts. LIF stimulation of myoblasts lead to rapid phosphoryla tion on tyrosine of STAT3 and of ERKs 1 and 2. Similarly, bFGF stimula tion of myoblasts resulted in the tyrosine phosphorylation of STAT3. H owever, unlike LIF, the bFGF induced tyrosine phosphorylation of STAT3 appeared cyclical, with recurrent peaks of phosphorylation even after prolonged exposure. By contrast, STAT1 remained unphosphorylated in m yoblasts treated with bFGF or LIF. In differentiated myotubes, LIF tre atment resulted in the tyrosine phosphorylation of both STAT3 and STAT 1, but ERK phosphorylation was not detectable, and bFGF treatment did not lead to STAT1 or STAT3 tyrosine phosphorylation. Therefore these o bservations suggest that disparate mitogens can activate similar downs tream effecters in proliferating myoblasts. (C) 1996 Wiley-Liss, Inc.