The mammalian Ste20-like kinase 2 (Mst2) modulates stress-induced cardiac hypertrophy

Min Zi, Arfa Maqsood, Sukhpal Prehar, Tamer M A Mohamed, Riham Abou-Leisa, Abigail Robertson, Elizabeth J. Cartwright, Simon G. Ray, Sangphil Oh, Dae Sik Lim, Ludwig Neyses, Delvac Oceandy

Research output: Contribution to journalArticlepeer-review


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. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)24275-24288
Number of pages13
JournalJournal of Biological Chemistry
Issue number35
Publication statusPublished - 2014


  • cardiac hypertrophy
  • cardiovascular disease
  • genetic polymorphism
  • signal transduction
  • transgenic mice


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