Cross-talk between the ERK and p70 S6 Kinase (S6K) Signaling Pathways
Cross-talk between the ERK and p70 S6 Kinase (S6K) Signaling Pathways
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ERK 和 p70 S6 激酶 (S6K) 信号通路之间的串扰
DOI：
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发表时间：
2001
影响因子：
4.8
通讯作者：
C. Proud
中科院分区：
文献类型：
--
作者：
Lijun Wang;I. Gout;C. Proud
α1肾上腺素能激动剂苯肾上腺素(PE)和胰岛素分别刺激心肌细胞蛋白质合成。PE对蛋白质合成的激活参与了心肌肥厚的发生。这里涉及的一个成分是p70 S6激酶1(S6K1)，它位于哺乳动物雷帕霉素靶标的下游，其调节被认为涉及磷脂酰肌醇3-激酶和蛋白激酶B(PKB)。S6K2是新近发现的S6K1同源基因，其调控机制尚不清楚。在这里，我们证明了在成年大鼠的心室肌细胞中，PE和胰岛素分别激活S6K2，激活分别是基础水平的3.5倍和5倍。雷帕霉素完全阻断PE或胰岛素对S6K2的激活。三种不同的MEK1/2抑制剂均可阻断PE诱导的S6K2的激活，而MEK1的表达可激活S6K2，但不影响p38丝裂原活化蛋白激酶和JNK信号通路，提示MEK/ERK信号通路在PE对S6K2的调控中起关键作用。PE不能激活PKB，显性负性PKB的表达不能阻断PE对S6K2的激活，说明PE诱导的S6K2激活不依赖于PKB。然而，这个PKB突变体确实部分阻断了胰岛素对S6K2的激活，表明这里需要PKB。另一种增生剂内皮素1也以MEK依赖的方式激活S6K2。我们的发现为MEK/ERK和S6K2之间新的信号联系提供了强有力的证据。
The α1-adrenergic agonist phenylephrine (PE) and insulin each stimulate protein synthesis in cardiomyocytes. Activation of protein synthesis by PE is involved in the development of cardiac hypertrophy. One component involved here is p70 S6 kinase 1 (S6K1), which lies downstream of mammalian target of rapamycin, whose regulation is thought to involve phosphatidylinositol 3-kinase and protein kinase B (PKB). S6K2 is a recently identified homolog of S6K1 whose regulation is poorly understood. Here we demonstrate that in adult rat ventricular cardiomyocytes, PE and insulin each activate S6K2, activation being 3.5- and 5-fold above basal, respectively. Rapamycin completely blocked S6K2 activation by either PE or insulin. Three different inhibitors of MEK1/2 abolished PE-induced activation of S6K2 whereas expression of constitutively active MEK1 activated S6K2, without affecting the p38 mitogen-activated protein kinase and JNK pathways, indicating that MEK/ERK signaling plays a key role in regulation of S6K2 by PE. PE did not activate PKB, and expression of dominant negative PKB failed to block activation of S6K2 by PE, indicating PE-induced S6K2 activation is independent of PKB. However, this PKB mutant did partially block S6K2 activation by insulin, indicating PKB is required here. Another hypertrophic agent, endothelin 1, also activated S6K2 in a MEK-dependent manner. Our findings provide strong evidence for novel signaling connections between MEK/ERK and S6K2.
DOI：
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发表时间：
1990-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
H. Shubeita;Patrick M. McDonough;A. N. Harris;Kirk U. Knowlton;C. C. Glembotski-C.;Joan Heller Brown;Kenneth R. Chien
通讯作者：
H. Shubeita;Patrick M. McDonough;A. N. Harris;Kirk U. Knowlton;C. C. Glembotski-C.;Joan Heller Brown;Kenneth R. Chien
DOI：
10.1073/pnas.95.4.1432
发表时间：
1998-02-17
影响因子：
11.1
作者：
Burnett, PE;Barrow, RK;Sabatini, DM
通讯作者：
Sabatini, DM