Extracellular signal-regulated kinase-1 and -2 respond differently to mitogenic and differentiative signaling pathways in myoblasts.
Extracellular signal-regulated kinase-1 and -2 respond differently to mitogenic and differentiative signaling pathways in myoblasts.
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细胞外信号调节激酶-1 和-2 对成肌细胞中的有丝分裂和分化信号通路有不同的反应。
DOI：
10.1210/mend.11.13.0036
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发表时间：
1997
影响因子：
--
通讯作者：
Charlotte A. Peterson
中科院分区：
文献类型：
--
作者：
D. Sarbassov;Linda Jones;Charlotte A. Peterson
在这份报告中，我们表明，细胞外信号调节激酶-1和-2（ERK-1和-2）的反应不同的信号，引起增殖和/或分化的成肌细胞使用C2 C12细胞系和非分化突变NFB 4细胞从他们。通过撤回血清的分化诱导使得C2 C12成肌细胞中的ERK对血清的再刺激相对不敏感。相反，C2 C12细胞的肌源性分化与依赖于胰岛素样生长因子II（IGF-II）自分泌环的ERK-2的持续激活相关。相比之下，在相同条件下培养的突变NFB 4细胞保持增殖，并表现出响应血清的ERK的稳健激活。类似地，在溶血磷脂酸（LPA）刺激后，Gi依赖性信号传导途径诱导NFB 4细胞中的ERK活化，但在C2 C12细胞中不诱导。在NFB 4细胞部分救援延长IGF-I治疗，ERK活性仍然响应于Gi依赖性LPA刺激，而救援的NFB 4细胞的肌生成素或MyoD的组成型表达，与IGF-II自分泌环的激活，使Gi信号通路难治性LPA刺激。在NFB 4细胞和IGF-I处理的NFB 4细胞中检测到相对高水平的G（α 12），其与响应性Gi信号传导相关。C2 C12和NFB 4成肌细胞中IGF-II自分泌环的激活或用IGF-II处理与G（α i2）的损失和Gi依赖性信号传导的抑制相关。因此，IGF-I和IGF-II激活不同的信号级联，IGF-II引起与G（α 12）蛋白下调相关的更强的分化效应。用IGF-I（成肌细胞的促有丝分裂信号）短期刺激NFB 4细胞也诱导ERK-1和ERK-2活化。用IGF-I瞬时刺激NFB 4细胞，同时用百日咳毒素阻断Gi蛋白的活化，导致分化的C2 C12细胞的ERK-2特征的优先活化，表明IGF-I诱导的增殖是Gi依赖性的，并且与导致分化的IGF-I信号传导途径分离。
In this report we show that extracellular signal-regulated kinase-1 and -2 (ERK-1 and -2) respond differently to signals that elicit proliferation and/or differentiation of myoblasts using the C2C12 cell line and nondifferentiating mutant NFB4 cells derived from them. Induction of differentiation by withdrawal of serum rendered ERKs in C2C12 myoblasts relatively insensitive to restimulation by serum. Instead, myogenic differentiation of C2C12 cells was associated with sustained activation of ERK-2 dependent on the insulin-like growth factor II (IGF-II) autocrine loop. By contrast, mutant NFB4 cells cultured under the same conditions remained proliferative and demonstrated robust activation of ERKs in response to serum. Similarly, a Gi-dependent signaling pathway induced activation of ERKs in NFB4 cells, but not in C2C12 cells, after stimulation by lysophosphatidic acid (LPA). In NFB4 cells partially rescued by prolonged IGF-I treatment, ERK activity remained responsive to Gi-dependent LPA stimulation, whereas rescue of NFB4 cells by constitutive expression of myogenin or MyoD, associated with activation of the IGF-II autocrine loop, rendered the Gi-signaling pathway refractory to LPA stimulation. Relatively high levels of G(alpha i2) were detected in NFB4 cells and IGF-I treated NFB4 cells, which correlated with responsive Gi signaling. Activation of the IGF-II autocrine loop in C2C12 and NFB4 myoblasts or treatment with IGF-II was associated with loss of G(alpha i2) and inhibition of Gi-dependent signaling. Thus, IGF-I and IGF-II activate distinct signaling cascades, with IGF-II eliciting a stronger differentiation effect correlated with down-regulation of G(alpha i2) protein. Short-term stimulation of NFB4 cells with IGF-I, a mitogenic signal for myoblasts, also induced ERK-1 and -2 activation. Transient stimulation of NFB4 cells with IGF-I while blocking activation of Gi-proteins is with pertussis toxin resulted in preferential activation of ERK-2 characteristic of differentiated C2C12 cells, suggesting that proliferation induced by IGF-I is Gi-dependent and separable from the IGF-I-signaling pathway that leads to differentiation.
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影响因子：
4.1
作者：
HER, JH;LAKHANI, S;WEBER, MJ
通讯作者：
WEBER, MJ
影响因子：
3.3
作者：
HEASLEY, LE;JOHNSON, GL
通讯作者：
JOHNSON, GL
DOI：
10.1016/s0021-9258(18)54918-8
发表时间：
1991-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Rossomando;J. Sanghera;L. Marsden;Michael J. Weber;S. Pelech;T. Sturgill
通讯作者：
A. Rossomando;J. Sanghera;L. Marsden;Michael J. Weber;S. Pelech;T. Sturgill
DOI：
10.1016/s0021-9258(18)82362-6
发表时间：
1993-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Davis
通讯作者：
R. Davis
胰岛素样生长因子-II (IGF-II) 优先结合 C2 成肌细胞中假定的 α2β2 IGF-II 受体类型。
DOI：
10.1111/j.1432-1033.1992.tb17183.x
发表时间：
1992
期刊：
European journal of biochemistry
影响因子：
--
作者：
Domeyne,A;Pinset,C;Montarras,D;Garandel,V;Rosenfeld,RG;Barenton,B
通讯作者：
Barenton,B