Characterization and function of MYPT2, a target subunit of myosin phosphatase in heart

Ryuji Okamoto, Takaaki Kato, Akira Mizoguchi, Nobuaki Takahashi, Tetsuya Nakakuki, Hideo Mizutani, Naoki Isaka, Kyoko Imanaka-Yoshida, Kozo Kaibuchi, Zhaojiang Lu, Katsuhide Mabuchi, Terenc Tao, David J. Hartshorne, Takeshi Nakano, Masaaki Ito

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Characterization of cardiac MYPT2 (an isoform of the smooth muscle phosphatase [MP] target subunit, MYPT1) is described. Several features of MYPT2 and MYPT1 were similar, including: a specific interaction with the catalytic subunit of type 1 phosphatase, δ isoform (PP1cδ); interaction of MYPT2 with the small heart-specific MP subunit; interaction of the C-terminal region of MYPT2 with the active form of RhoA; phosphorylation by Rho-kinase at an inhibitory site, Thr646 and thiophosphorylation at Thr646 inhibited activity of the MYPT2-PP1cδ complex. MYPT2 activated PP1cδ activity, using light chains from smooth and cardiac muscle, by reducing Km and increasing kcat. The extent of activation (kcat) was greater than for MYPT1 and could reflect distinct N-terminal sequences in the two MYPT isoforms. Adenovirus-mediated gene transfer of MYPT2 and PP1cδ reduced the phosphorylation level of cardiac light chains following stimulation with A23187. Overexpression of MYPT2 and PP1cδ blocked the angiotensin II-induced sarcomere organization in cultured cardiomyocytes. Electron microscopy indicated locations of MYPTs, at, or close to, the Z-line, the A band and mitochondria. Similarity of the two MYPT isoforms suggests common enzymatic mechanisms and regulation. Cardiac myosin is a substrate for the MYPT2 holoenzyme, but the Z-line location raises the possibility of other substrates.

Original languageEnglish
Pages (from-to)1408-1416
Number of pages9
JournalCellular Signalling
Volume18
Issue number9
DOIs
Publication statusPublished - 09-2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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