当前位置： SCI文献检索 > JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY期刊下所有文献 > Regulation of mTOR and S6K1 activation by the nPKC isoforms, PKCepsilon and PKCdelta, in adult cardiac muscle cells.

Regulation of mTOR and S6K1 activation by the nPKC isoforms, PKCepsilon and PKCdelta, in adult cardiac muscle cells.

Abstract：

:Activation of both mTOR and its downstream target, S6K1 (p70 S6 kinase) have been implicated to affect cardiac hypertrophy. Our earlier work, in a feline model of 1-48 h pressure overload, demonstrated that mTOR/S6K1 activation occurred primarily through a PKC/c-Raf pathway. To further delineate the role of specific PKC isoforms on mTOR/S6K1 activation, we utilized primary cultures of adult feline cardiomyocytes in vitro and stimulated with endothelin-1 (ET-1), phenylephrine (PE), TPA, or insulin. All agonist treatments resulted in S2248 phosphorylation of mTOR and T389 and S421/T424 phosphorylation of S6K1, however only ET-1 and TPA-stimulated mTOR/S6K1 activation was abolished with infection of a dominant negative adenoviral c-Raf (DN-Raf) construct. Expression of DN-PKC(epsilon) blocked ET-1-stimulated mTOR S2448 and S6K1 S421/T424 and T389 phosphorylation but had no effect on insulin-stimulated S6K1 phosphorylation. Expression of DN-PKC(delta) or pretreatment of cardiomyocytes with rottlerin, a PKC(delta) specific inhibitor, blocked both ET-1 and insulin stimulated mTOR S2448 and S6K1 T389 phosphorylation. However, treatment with Gö6976, a specific classical PKC (cPKC) inhibitor did not affect mTOR/S6K1 activation. These data indicate that: (i) PKC(epsilon) is required for ET-1-stimulated T421/S424 phosphorylation of S6K1, (ii) both PKC(epsilon) and PKC(delta) are required for ET-1-stimulated mTOR S2448 and S6K1 T389 phosphorylation, (iii) PKC(delta) is also required for insulin-stimulated mTOR S2448 and S6K1 T389 phosphorylation. Together, these data delineate both distinct and combinatorial roles of specific PKC isoforms on mTOR and S6K1 activation in adult cardiac myocytes following hypertrophic stimulation.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Moschella PC,Rao VU,McDermott PJ,Kuppuswamy D

doi

10.1016/j.yjmcc.2007.09.015

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

754-66

issue

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(07)01244-8

journal_volume

pub_type

杂志文章

在线工具

Regulation of mTOR and S6K1 activation by the nPKC isoforms, PKCepsilon and PKCdelta, in adult cardiac muscle cells.