SGK1-Sensitive Regulation of Cyclin-Dependent Kinase Inhibitor 1B (p27) in Cardiomyocyte Hypertrophy

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Jakob VoelklFlorian Lang

Abstract

The serum- and glucocorticoid-inducible kinase SGK1 participates in the orchestration of cardiac hypertrophy and remodeling. Signaling linking SGK1 activity to cardiac remodeling is, however, incompletely understood. SGK1 phosphorylation targets include cyclin-dependent kinase inhibitor 1B (p27), a protein which suppresses cardiac hypertrophy. The present study explored how effects of SGK1 on nuclear p27 localization might modulate the hypertrophic response in cardiomyocytes. Experiments were performed in HL-1 cardiomyocytes and in SGK1-deficient (sgk1-/-) and corresponding wild-type (sgk1+/+) mice following pressure overload by transverse aortic constriction (TAC). Transcript levels were quantified by RT-PCR, protein abundance by Western blotting and protein localization by confocal microscopy. In HL-1 cardiomyocytes, overexpression of constitutively active SGK1 (SGK1S422D) but not of inactive SGK1 (SGK1K127N) increased significantly the cell size and transcript levels encoding Acta1, a molecular marker of hypertrophy. Those effects were paralleled by almost complete relocation of p27 in the cytoplasm. Treatment of HL-1 cardiomyocytes with isoproterenol was followed by up-regulation of SGK1 expression. Moreover, isoproterenol ...Continue Reading

Citations

Feb 2, 2019·Pflügers Archiv : European journal of physiology·Nadeshda SchelskiIoana Alesutan
Mar 20, 2019·Cellular and Molecular Life Sciences : CMLS·Jakob VoelklIoana Alesutan
Jun 12, 2018·The Journal of Clinical Investigation·Jakob VoelklIoana Alesutan
Jan 23, 2021·Clinical Science·Trang Thi Doan LuongIoana Alesutan
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Florian LangMadhuri S Salker
Sep 27, 2021·Pflügers Archiv : European journal of physiology·Barbara MoserJakob Voelkl

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