Toshio Kitazawa, Ph.D.
Senior Scientist
Signal Transductions in Smooth Muscle
Email: kitazawa at bbri.org

Research Summary
The functions of many of our internal organs including blood vessels rely on the delicate control of smooth muscle contraction. Smooth muscle disorders contribute to many diseases, such as hypertension and asthma. Smooth muscle contraction/relaxation cycles require reversible phosphorylation of myosin regulatory light chain by myosin light chain kinase (MLCK) and myosin phosphatase (MLCP). We have proposed that most smooth muscle stimulants cause an up-regulation of MLCK and a down-regulation of MLCP, resulting in a large sustained contraction. In contrast, relaxants such as nitric oxide cause a down-regulation of MLCK and an up-regulation of MLCP. We are investigating molecular mechanisms for in situ regulation of MLCK and MLCP in order to explore the pathological mechanism in smooth muscles.

Selected Publications
Dimopoulos, G. J., Semba, S., Kitazawa, K., Eto, M. & Kitazawa, T. (2007). Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle. Circ Res 100:121-9.
This paper was selected for “Editorial” of the Circ. Res.

Eto M, Kitazawa T, Matsuzawa F, Aikawa S, Kirkbride JA, Isozumi N, Nishimura Y, Brautigan DL, Ohki SY. (2007) Phosphorylation-induced conformational switching of CPI-17 produces a potent myosin phosphatase inhibitor. Structure. 15(12):1591-602.

Ai X, Kitazawa T, Do AT, Kusche-Gullberg M, Labosky PA, Emerson CP Jr. (2007) SULF1 and SULF2 regulate heparan sulfate-mediated GDNF signaling for esophageal innervation. Development. 134(18):3327-38.

Woodsome TP, Polzin A, Kitazawa K, Eto M, Kitazawa T. (2006) Agonist- and depolarization-induced signals for myosin light chain phosphorylation and force generation of cultured vascular smooth muscle cells. J Cell Sci. 119(Pt 9), 1769-80.

Eto M, Kitazawa T, Brautigan DL. (2004) Phosphoprotein inhibitor CPI-17 specificity depends on allosteric regulation of protein phosphatase-1 by regulatory subunits. Proc Natl Acad Sci U S A. 101(24), 8888-93.

Kitazawa T, Polzin AN, Eto M. (2004) CPI-17-deficient smooth muscle of chicken. J Physiol. 557(Pt 2), 515-28.

PubMed:
Click here for a list of publications (searches the National Library of Medicine's PubMed database.)