MECHANICAL-STRESS ACTIVATES PROTEIN-KINASE CASCADE OF PHOSPHORYLATION IN NEONATAL RAT CARDIAC MYOCYTES

被引：180

作者：

YAMAZAKI, T ^{[1
]}

KOMURO, I ^{[1
]}

KUDOH, S ^{[1
]}

ZOU, YZ ^{[1
]}

SHIOJIMA, I ^{[1
]}

MIZUNO, T ^{[1
]}

TAKANO, H ^{[1
]}

HIROI, Y ^{[1
]}

UEKI, K ^{[1
]}

TOBE, K ^{[1
]}

KADOWAKI, T ^{[1
]}

NAGAI, R ^{[1
]}

YAZAKI, Y ^{[1
]}

机构：

[1] UNIV TOKYO, SCH MED, DEPT MED 3, BUNKYO KU, TOKYO 113, JAPAN

来源：

JOURNAL OF CLINICAL INVESTIGATION | 1995年 / 96卷 / 01期

关键词：

CARDIAC HYPERTROPHY; SIGNAL TRANSDUCTION; RAF-1; KINASE; MITOGEN-ACTIVATED PROTEIN KINASE KINASE; MITOGEN-ACTIVATED PROTEIN KINASE;

D O I：

10.1172/JCI118054

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

We have previously shown that stretching cardiac myocytes evokes activation of protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and 90-kD ribosomal S6 kinase (p90(rsk)). To clarify the signal transduction pathways from external mechanical stress tb nuclear gene expression in stretch-induced cardiac hypertrophy, we have elucidated protein kinase cascade of phosphorylation by examining the time course of activation of MAP kinase kinase kinases (MAPKKKs), MAP kinase kinase (MAPKK), MAPKs, and p90(rsk) in neonatal rat cardiac myocytes. Mechanical stretch transiently increased the activity of MAPKKKs. An increase in MAPKKKs activity was first detected at 1 min and maximal activation was observed at 2 min after stretch, The activity of MAPKK was increased by stretch from 1-2 min, with a peak at 5 min after stretch, In addition, MAPKs and p90(rsk) were maximally activated at 8 min and at 10 similar to 30 min after stretch, respectively, Raf-1 kinase (Raf-l) and (MAPK/extracellular signal-regulated kinase) kinase kinase (MEKK), both of which have MAPKKK activity, were also activated by stretching cardiac myocytes for 2 min, The angiotensin II receptor antagonist partially suppressed activation of Raf-1 and MAPKs by stretch, The stretch-induced hypertrophic responses such as activation of Raf-1 and MAPKs and an increase in amino acid uptake was partially dependent on PKC, while a PKC inhibitor completely abolished MAPK activation by angiotensin II. These results suggest that mechanical stress activates the protein kinase cascade of phosphorylation in cardiac myocytes in the order of Raf-1 and MEKK, MAPKK, MAPKs and p90(rsk), and that angiotensin II, which may be secreted from stretched myocytes, may be partly involved in stretch-induced hypertrophic responses by activating PKC.

引用

页码：438 / 446

页数：9

共 48 条

[1]

Levy D., Garrison R.J., Savage D.D., Kannel W.B., Castelli W.P., Prognostic implications of echocardiographically determined left ventricular mass in the Framingham heart study, N. Engl. J. Med., 322, pp. 1561-1566, (1990)

[2]

Komuro I., Yazaki Y., Control of cardiac gene expression by mechanical stress, Annu. Rev. Physiol., 55, pp. 55-75, (1993)

[3]

Komuro I., Kurabayashi M., Takaku F., Yazaki Y., Expression of cellular oncogenes in the myocardium during the developmental stage and pressure overload hypertrophy of the rat heart, Circ. Res., 62, pp. 1075-1079, (1988)

[4]

Mulvagh S.L., Michael L.H., Perryman M.B., Roberts R., Schneider M.D., A hemodynamic load in vivo induces cardiac expression of the cellular oncogene, c-myc, Biochem. Biophys. Res. Commun., 147, pp. 627-636, (1987)

[5]

Komuro I., Kaida T., Shibazaki Y., Kurabayashi M., Takaku F., Yazaki Y., Stretching cardiac myocytes stimulates proto-oncogene expression, J. Biol. Chem., 265, pp. 3595-3598, (1990)

[6]

Komuro I., Katoh Y., Kaida T., Shibazaki Y., Kurabayashi M., Takaku F., Yazaki Y., Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes, J. Biol. Chem., 266, pp. 1265-1268, (1991)

[7]

Yamazaki T., Tobe K., Hoh E., Maemura K., Kaida T., Komuro I., Tamemoto H., Kadowaki T., Nagai R., Yazaki Y., Mechanical loading activates mitogen-activated protein kinase and S6 peptide kinase in cultured rat cardiac myocytes, J. Biol. Chem., 268, pp. 12069-12076, (1993)

[8]

Gomez N., Cohen P., Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases, Nature (Lond.), 353, pp. 170-173, (1991)

[9]

Ahn N.G., Seger R., Bratlien R.L., Diltz C.D., Tonks N.K., Krebs E.G., Multiple components in an EGF-stimulated protein kinase cascade. in vitro activation of a MBP/MAP2 kinase, J. Biol. Chem., 266, pp. 4220-4227, (1991)

[10]

Matsuda S., Kosako H., Takenaka K., Moriyama K., Sakai H., Akiyama T., Gotoh Y., Nishida E., Xenopus MAP kinase activator: Identification and function as a key intermediate in the phosphorylation cascade, EMBO (Eur. Mol. Biol. Org.) J., 11, pp. 973-982, (1992)

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