Megeney L A, Perry R L, LeCouter J E, Rudnicki M A
Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada.
Dev Genet. 1996;19(2):139-45. doi: 10.1002/(SICI)1520-6408(1996)19:2<139::AID-DVG5>3.0.CO;2-A.
Different mitogens elicit similar effects on growth and differentiation of skeletal muscle, suggesting that potential overlap exists in the signaling cascades activated by such factors. To investigate this possibility, we examined the status of STAT and ERK proteins in C2C12 myoblasts and myotubes following stimulation with bFGF or LIF. Both STAT1 and STAT3 as well as ERK1 and ERK2 proteins were detectable in extracts of myoblasts. LIF stimulation of myoblasts lead to rapid phosphorylation on tyrosine of STAT3 and of ERKs 1 and 2. Similarly, bFGF stimulation of myoblasts resulted in the tyrosine phosphorylation of STAT3. However, 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 myoblasts treated with bFGF or LIF. In differentiated myotubes, LIF treatment resulted in the tyrosine phosphorylation of both STAT3 and STAT1, but ERK phosphorylation was not detectable, and bFGF treatment did not lead to STAT1 or STAT3 tyrosine phosphorylation. Therefore these observations suggest that disparate mitogens car activate similar downstream effectors in proliferating myoblasts.
不同的促有丝分裂原对骨骼肌的生长和分化产生相似的影响，这表明这些因子激活的信号级联反应可能存在潜在重叠。为了研究这种可能性，我们检测了用碱性成纤维细胞生长因子（bFGF）或白血病抑制因子（LIF）刺激后C2C12成肌细胞和肌管中信号转导和转录激活因子（STAT）及细胞外信号调节激酶（ERK）蛋白的状态。在成肌细胞提取物中可检测到STAT1和STAT3以及ERK1和ERK2蛋白。LIF刺激成肌细胞导致STAT3以及ERK1和ERK2的酪氨酸快速磷酸化。同样，bFGF刺激成肌细胞导致STAT3的酪氨酸磷酸化。然而，与LIF不同，bFGF诱导的STAT3酪氨酸磷酸化呈周期性，即使长时间暴露后磷酸化仍有反复峰值。相比之下，在用bFGF或LIF处理的成肌细胞中STAT1仍未磷酸化。在分化的肌管中，LIF处理导致STAT3和STAT1的酪氨酸磷酸化，但未检测到ERK磷酸化，且bFGF处理未导致STAT1或STAT3的酪氨酸磷酸化。因此，这些观察结果表明，不同的促有丝分裂原可在增殖的成肌细胞中激活相似的下游效应器。
