*Department of Physiology
Life Sciences | Medicine and Health Sciences
Myosin II phosphorylation-dependent cell motile events are regulated by myosin light-chain (MLC) kinase and MLC phosphatase (MLCP). Recent studies have revealed myosin phosphatase targeting subunit (MYPT1), a myosin-binding subunit of MLCP, plays a critical role in MLCP regulation. Here we report the new regulatory mechanism of MLCP via the interaction between 14-3-3 and MYPT1. The binding of 14-3-3beta to MYPT1 diminished the direct binding between MYPT1 and myosin II, and 14-3-3beta overexpression abolished MYPT1 localization at stress fiber. Furthermore, 14-3-3beta inhibited MLCP holoenzyme activity via the interaction with MYPT1. Consistently, 14-3-3beta overexpression increased myosin II phosphorylation in cells. We found that MYPT1 phosphorylation at Ser472 was critical for the binding to 14-3-3. Epidermal growth factor (EGF) stimulation increased both Ser472 phosphorylation and the binding of MYPT1-14-3-3. Rho-kinase inhibitor inhibited the EGF-induced Ser472 phosphorylation and the binding of MYPT1-14-3-3. Rho-kinase specific siRNA also decreased EGF-induced Ser472 phosphorylation correlated with the decrease in MLC phosphorylation. The present study revealed a new RhoA/Rho-kinase-dependent regulatory mechanism of myosin II phosphorylation by 14-3-3 that dissociates MLCP from myosin II and attenuates MLCP activity.
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Citation: Mol Biol Cell. 2008 Mar;19(3):1062-71. Epub 2007 Dec 19. Link to article on publisher's site
DOI of Published Version
Molecular biology of the cell
Koga, Yasuhiko and Ikebe, Mitsuo, "A Novel Regulatory Mechanism of Myosin Light Chain Phosphorylation via Binding of 14-3-3 to Myosin Phosphatase" (2007). Open Access Articles. 1316.