Article (Scientific journals)
The mammalian Ste20-like kinase 2 (Mst2) modulates stress-induced cardiac hypertrophy.
Zi, Min; Maqsood, Arfa; Prehar, Sukhpal et al.
2014In The Journal of biological chemistry, 289 (35), p. 24275-88
Peer reviewed
 

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Keywords :
Animals; Apoptosis; Cardiomegaly/enzymology/pathology/physiopathology; Cell Proliferation; Humans; In Situ Nick-End Labeling; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Phenylephrine/adverse effects; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins c-raf/metabolism; Stress, Physiological; Cardiac Hypertrophy; Cardiovascular Disease; Genetic Polymorphism; Signal Transduction; Transgenic Mice
Abstract :
[en] The Hippo signaling pathway has recently moved to center stage in cardiac research because of its key role in cardiomyocyte proliferation and regeneration of the embryonic and newborn heart. However, its role in the adult heart is incompletely understood. We investigate here the role of mammalian Ste20-like kinase 2 (Mst2), one of the central regulators of this pathway. Mst2(-/-) mice showed no alteration in cardiomyocyte proliferation. However, Mst2(-/-) mice exhibited a significant reduction of hypertrophy and fibrosis in response to pressure overload. Consistently, overexpression of MST2 in neonatal rat cardiomyocytes significantly enhanced phenylephrine-induced cellular hypertrophy. Mechanistically, Mst2 positively modulated the prohypertrophic Raf1-ERK1/2 pathway. However, activation of the downstream effectors of the Hippo pathway (Yes-associated protein) was not affected by Mst2 ablation. An initial genetic study in mitral valve prolapse patients revealed an association between a polymorphism in the human MST2 gene and adverse cardiac remodeling. These results reveal a novel role of Mst2 in stress-dependent cardiac hypertrophy and remodeling in the adult mouse and likely human heart.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Zi, Min
Maqsood, Arfa
Prehar, Sukhpal
Mohamed, Tamer M. A.
Abou-Leisa, Riham
Robertson, Abigail
Cartwright, Elizabeth J.
Ray, Simon G.
Oh, Sangphil
Lim, Dae-Sik
Neyses, Ludwig ;  University of Luxembourg > Rectorate > Research Service
Oceandy, Delvac
External co-authors :
yes
Language :
English
Title :
The mammalian Ste20-like kinase 2 (Mst2) modulates stress-induced cardiac hypertrophy.
Publication date :
2014
Journal title :
The Journal of biological chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Volume :
289
Issue :
35
Pages :
24275-88
Peer reviewed :
Peer reviewed
Commentary :
(c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
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