J. Cell Biol., Volume 144, Number 4, February 22, 1999 735-744

Activation of Myosin Phosphatase Targeting Subunit by Mitosis-specific Phosphorylation

Go Totsukawa,^* Yoshihiko Yamakita,^* Shigeko Yamashiro,^* Hiroshi Hosoya, David J. Hartshorne,^§ and Fumio Matsumura^*

^* Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08855;  Department of Biological Science, Faculty of Science, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8526, Japan; and ^§ Muscle Biology Group, University of Arizona, Tucson, Arizona 85721

It has been demonstrated previously that during mitosis the sites of myosin phosphorylation are switched between the inhibitory sites, Ser 1/2, and the activation sites, Ser 19/Thr 18 (Yamakita, Y., S. Yamashiro, and F. Matsumura. 1994. J. Cell Biol. 124:129- 137; Satterwhite, L.L., M.J. Lohka, K.L. Wilson, T.Y. Scherson, L.J. Cisek, J.L. Corden, and T.D. Pollard. 1992. J. Cell Biol. 118:595-605), suggesting a regulatory role of myosin phosphorylation in cell division. To explore the function of myosin phosphatase in cell division, the possibility that myosin phosphatase activity may be altered during cell division was examined. We have found that the myosin phosphatase targeting subunit (MYPT) undergoes mitosis-specific phosphorylation and that the phosphorylation is reversed during cytokinesis. MYPT phosphorylated either in vivo or in vitro in the mitosis-specific way showed higher binding to myosin II (two- to threefold) compared to MYPT from cells in interphase. Furthermore, the activity of myosin phosphatase was increased more than twice and it is suggested this reflected the increased affinity of myosin binding. These results indicate the presence of a unique positive regulatory mechanism for myosin phosphatase in cell division. The activation of myosin phosphatase during mitosis would enhance dephosphorylation of the myosin regulatory light chain, thereby leading to the disassembly of stress fibers during prophase. The mitosis-specific effect of phosphorylation is lost on exit from mitosis, and the resultant increase in myosin phosphorylation may act as a signal to activate cytokinesis.

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