Differential Activation of p70 and p85 S6 Kinase Isoforms during Cardiac Hypertrophy in the Adult Mammal
An adult feline right ventricular pressure overload (RVPO) model was used to examine the two S6 kinase (S6K) isoforms, p70S6K and p85S6K, that are involved in translational and transcriptional activation. Biochemical and confocal microscopy analyses at the level of the cardiocyte revealed that p70S6...
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Published in | The Journal of biological chemistry Vol. 273; no. 38; pp. 24610 - 24619 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
18.09.1998
American Society for Biochemistry and Molecular Biology |
Subjects | |
Online Access | Get full text |
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Summary: | An adult feline right ventricular pressure overload (RVPO) model was used to examine the two S6 kinase (S6K) isoforms, p70S6K and p85S6K, that are involved in translational and transcriptional activation. Biochemical and confocal microscopy analyses at the level of the cardiocyte revealed that p70S6K is present predominantly in the cytosol, substantially activated in 1-h RVPO (>12 fold), and phosphorylated in the pseudosubstrate domain at the Ser-411, Thr-421, and Ser-424 sites. p85S6K, which was localized exclusively in the nucleus, showed activation subsequent to p70S6K, with a sustained increase in phosphorylation for up to 48 h of RVPO at equivalent sites of p70S6K, Thr-421 and Ser-424, but not at Ser-411. Neither isoform translocated between the cytosol and the nucleus. Further studies to determine potential upstream elements of S6K activation revealed: (i) similar time course of activation for protein kinase C isoforms (α, γ, and ε) and c-Raf, (ii) absence of accompanying phosphatidylinositol 3-kinase activation, (iii) activation of c-Src subsequent to p70S6K, and (iv) similar changes in adult cardiocytes after treatment with 12-O-tetradecanoylphorbol-13-acetate. Thus, these studies suggest that a protein kinase C-mediated pathway couples pressure overload to growth induction via differential activation of S6K isoforms in cardiac hypertrophy. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.273.38.24610 |