Effect of Contraction on Mitogen-activated Protein Kinase Signal Transduction in Skeletal Muscle

Effect of Contraction on Mitogen-activated Protein Kinase Signal Transduction in Skeletal Muscle
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收缩对骨骼肌丝裂原激活蛋白激酶信号转导的影响

DOI:
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发表时间:
2000
影响因子:
4.8
通讯作者:
J. Zierath
J. Zierath
中科院分区:
生物学2区
文献类型:
--
作者:
J. Ryder;Roger Fahlman;H. Wallberg;D. Alessi;A. Krook;J. Zierath

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越来越多的证据表明,丝裂原激活蛋白激酶(MAPK)信号转导的激活介导了运动后肌肉基因表达的变化。然而,人们对 MAPK 响应肌肉收缩的上游或下游调节知之甚少。在这里,我们证明离体肌肉收缩会刺激细胞外信号调节激酶 1 和 2 (ERK1/2) 以及 p38MAPK 磷酸化。 ERK1/2 或 p38MAPK 的磷酸化不受蛋白激酶 C 抑制 (GF109203X) 的影响,表明蛋白激酶 C 不参与介导收缩诱导的 MAPK 信号传导。分别用 PD98059(MAPK 激酶抑制剂)和 SB203580(p38MAPK 抑制剂)预处理完全抑制 ERK1/2 和 p38MAPK 收缩刺激的磷酸化。肌肉收缩还激活 MAPK 下游靶标 p90 核糖体 S6 激酶 (p90Rsk)、MAPK 激活蛋白激酶 2 (MAPKAP-K2) 以及丝裂原和应激激活蛋白激酶 1 (MSK1)。 PD98059 或 SB203580 的使用表明,p90Rsk 和 MAPKAP-K2 的刺激分别最接近地反映了 ERK 和 p38MAPK 的刺激。刺激 MSK1 收缩骨骼肌需要激活 ERK 和 p38MAPK。这些数据表明,与全身影响无关的肌肉收缩会激活 MAPK 信号传导。此外,我们首次证明收缩活动会刺激 MAPKAP-K2 和 MSK1。
Growing evidence suggests that activation of mitogen-activated protein kinase (MAPK) signal transduction mediates changes in muscle gene expression in response to exercise. Nevertheless, little is known about upstream or downstream regulation of MAPK in response to muscle contraction. Here we show that ex vivo muscle contraction stimulates extracellular signal-regulated kinase 1 and 2 (ERK1/2), and p38MAPK phosphorylation. Phosphorylation of ERK1/2 or p38MAPK was unaffected by protein kinase C inhibition (GF109203X), suggesting that protein kinase C is not involved in mediating contraction-induced MAPK signaling. Contraction-stimulated phosphorylation of ERK1/2 and p38MAPK was completely inhibited by pretreatment with PD98059 (MAPK kinase inhibitor) and SB203580 (p38MAPKinhibitor), respectively. Muscle contraction also activated MAPK downstream targets p90 ribosomal S6 kinase (p90Rsk), MAPK-activated protein kinase 2 (MAPKAP-K2), and mitogen- and stress-activated protein kinase 1 (MSK1). Use of PD98059 or SB203580 revealed that stimulation of p90Rsk and MAPKAP-K2 most closely reflects ERK and p38MAPK stimulation, respectively. Stimulation of MSK1 in contracting skeletal muscle required the activation of both ERK and p38MAPK. These data demonstrate that muscle contraction, separate from systemic influence, activates MAPK signaling. Furthermore, we are the first to show that contractile activity stimulates MAPKAP-K2 and MSK1.
DOI: 10.1126/science.7914033
发表时间: 1994-08-05
期刊: SCIENCE
影响因子: 56.9
作者:
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发表时间: 1993-06-25
期刊: SCIENCE
影响因子: 56.9
作者:
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DOI: --
发表时间: 1994
期刊: The Journal of biological chemistry
影响因子: --
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