Sherwood D J, Dufresne S D, Markuns J F, Cheatham B, Moller D E, Aronson D, Goodyear L J
Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
Am J Physiol. 1999 May;276(5):E870-8. doi: 10.1152/ajpendo.1999.276.5.E870.
To study the effects of contractile activity on mitogen-activated protein kinase (MAP kinase), p70 S6 kinase (p70(S6K)), and Akt kinase signaling in rat skeletal muscle, hindlimb muscles were contracted by electrical stimulation of the sciatic nerve for periods of 15 s to 60 min. Contraction resulted in a rapid and transient activation of Raf-1 and MAP kinase kinase 1, a rapid and more sustained activation of MAP kinase and the 90-kDa ribosomal S6 kinase 2, and a dramatic increase in c-fos mRNA expression. Contraction also resulted in an apparent increase in the association of Raf-1 with p21Ras, although stimulation of MAP kinase signaling occurred independent of Shc, IRS1, and IRS2 tyrosine phosphorylation or the formation of Shc/Grb2 or IRS1/Grb2 complexes. Insulin was considerably less effective than contraction in stimulating the MAP kinase pathway. However, insulin, but not contraction, increased p70(S6K) and Akt activities in the muscle. These results demonstrate that contraction-induced activation of the MAP kinase pathway is independent of proximal steps in insulin and/or growth factor-mediated signaling, and that contraction and insulin have discordant effects with respect to the activation of the MAP kinase pathway vs. p70(S6K) and Akt. Of the numerous stimulators of MAP kinase in skeletal muscle, contractile activity emerges as a potent and physiologically relevant activator of MAP kinase signaling, and thus activation of this pathway is likely to be an important molecular mechanism by which skeletal muscle cells transduce mechanical and/or biochemical signals into downstream biological responses.
为研究收缩活动对大鼠骨骼肌中丝裂原活化蛋白激酶（MAP激酶）、p70 S6激酶（p70(S6K)）和Akt激酶信号传导的影响，通过电刺激坐骨神经使后肢肌肉收缩15秒至60分钟。收缩导致Raf-1和MAP激酶激酶1快速短暂激活，MAP激酶和90 kDa核糖体S6激酶2快速且更持久地激活，以及c-fos mRNA表达显著增加。收缩还导致Raf-1与p21Ras的结合明显增加，尽管MAP激酶信号传导的刺激独立于Shc、IRS1和IRS2酪氨酸磷酸化或Shc/Grb2或IRS1/Grb2复合物的形成。胰岛素在刺激MAP激酶途径方面远不如收缩有效。然而，胰岛素而非收缩增加了肌肉中p70(S6K)和Akt的活性。这些结果表明，收缩诱导的MAP激酶途径激活独立于胰岛素和/或生长因子介导信号传导的近端步骤，并且收缩和胰岛素在MAP激酶途径与p70(S6K)和Akt的激活方面具有不一致的作用。在骨骼肌中众多的MAP激酶刺激物中，收缩活动成为MAP激酶信号传导的一种强大且生理相关的激活剂，因此该途径的激活可能是骨骼肌细胞将机械和/或生化信号转化为下游生物学反应的重要分子机制。
