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Thomas Jefferson University - Masumi Eto, Ph.D.
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Masumi Eto, Ph.D.
Physiology
Department of Molecular Physiology and Biophysics
Kimmel Cancer Center
Associate Professor
Appointed: 2006
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Mailing Address
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1020 Locust Street, 436 JAH
Philadelphia, Pennsylvania 19107
United States
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Expertise and Research Interests
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>>>PHOSPHATASE SIGNALING AND CYTOSKELETAL REGULATION<<<
Current Member: JAH 436, Phone 215-503-7892
> Garbo D. Young, Lab Specialist/MS student
> Jee In Kim, Postdoc Fellow
Previous Members
> Archana Verma, Postdoc Fellow
> Jason A. Kirkbride, Senior Research Associate
> Shawna Dougherty, MS student
> Yongtong Zhao, Senior Research Associate
Research Overview:
The long-term goal of our research is to understand signal transduction mediated by protein phosphorylation in cell motility, which is critical in every aspect of Vascular Biology and Cancer Biology. Cell motility is governed by dynamic regulation of cytoskeleton via protein phosphorylation and dephosphorylation. Protein phosphatases and cytoskeletal proteins play dominant roles in controlling cell motility, although underlying mechanisms have yet to be understood. Current research projects are designed to unveil molecular aspects in the regulation of smooth muscle contraction and cell migration, using a multidisciplinary approach, including molecular physiology, biophysics, and cell imaging.
Research Projects are to:
1. Unveil the mechanisms underlying the regulation of smooth muscle contraction/relaxation via myosin phosphatase:
Myosin phosphatase is a heterotrimeric protein, consisting of protein phosphatase-1 (PP1) and MYPT1 regulatory subunit. Myosin phosphatase activity is inhibited in response to agonist stimulation that is required for a quick and robust contraction. Therefore, studying on the regulation of myosin phosphatase is important to reveal the signal transduction in smooth muscle contraction. Current research is to gain a new insight into cellular function and regulatory mechanism of a specific inhibitor protein, CPI-17, and MYPT1 subunit in smooth muscle in TIME AND SPACE, using recombinant proteins and microscopic technique.
2. Understand regulation of cellular PP1 by phosphatome approach:
Ser/Thr protein phosphatase-1 (PP1) exists as variety type of holoenzymes, consisting of a catalytic subunit and a regulatory/targeting subunit. In addition, over 10 PP1 inhibitory proteins are expressed in mammalian cells. We hypothesize that that each PP1 inhibitor recognizes specific pool of target PP1 complexes to control particular cellular events. Currently, we seek the target PP1 complex of several PP1 inhibitors using a proteomic approach, PHOSPHATOME.
3. Uncover the function of a cytoskeletal protein, filamin-B and its genetic mutants in cell migration:
Filamin was discovered as an actin binding protein and tethers various proteins to cytoskeletons. Mutations of B-isoform of filamin at actin binding domain are associated with genetic disorders, such as Larsen syndrome, suggesting an importance in normal development. We are testing the hypothesis that the tethering function of filamin-B is necessary for cytoskeletal reorganization during embryonic cell migration. We discovered novel filamin B-binding proteins by yeast two-hybrid screening. Current project is to understand roles of these filamin-binding proteins in regulation of cytoskeletal reorganization and cell migration.
Collaborating project: Signal transduction in migration of melanoma cells:
Melanoma cells produce interleukin-10 (IL10) that suppresses host immune response. Understanding of the signaling pathway in IL10 production is expected to expose potential targets of anti-melanoma therapeutics. We investigate molecular mechanisms of IL10 production in human melanoma cells, focusing on STAT3 and ERK1/2 pathways.
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Keywords
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Cell motility; Smooth muscle contraction; Artery; Airway; Hypertension; Asthma; Cancer; Signal Transduction; G-protein; Myosin; Phosphorylation; Cytoskeleton; Protein Kinase C; Rho-kinase; Myosin Phosphatase; Protein Phosphatase; CPI-17; PHI-1; Filamin; STAT3; ERK1/2; Enzyme regulation; Cell Imaging; Fluorescence microscope; FRET imaging; Fluorescence Polarization; Structural biology; NMR spectroscopy; Computer modeling; Proteome; Phosphatome; Protein purification; Yeast two-hybrid; Molecular Physiology; Vascular Biology; Biochemistry; Cell Biology
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Publications
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- Selected Publication (2005 - present) * Corresponding Author
- 36. Matsuzawa, F., Aikawa, S., Ohki, S., and Eto*, M. (2005) Phospho-pivot Modeling Predicts Specific Interactions of Protein Phosphatase-1 with a Phospho-inhibitor Protein CPI-17. J. Biochem. 137, 633-641.
- 37. Pang, H., Guo, Z., Su, W., Xie, Z., Eto, M., and Gong*, M. C. (2005) RhoA/Rho kinase mediates thrombin- and U-46619-induced phosphorylation of a myosin phosphatase inhibitor, CPI-17, in vascular smooth muscle cells. Am. J. Physiol. Cell Physiol., 289, C352-C360.
- 38. Matsuzawa, F., Ohki, S., Aikawa, S., and Eto*, M. (2005) Computational simulation for interaction of nano-molecules. Science and Technology of Advanced Materials, 6, 463-467.
- 39. Eto, M., Jason A. Kirkbride, and Brautigan*, D. L. (2005) Assembly of MYPT1 with protein phosphatase-1 in fibroblasts redirects localization and reorganizes the actin cytoskeleton. Cell Motil and Cytoskel, 62, 100-109.
- 40. Woodsome T. P., Polzin, A., Kitazawa, K., Eto, M., and 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, 1769-1780.
- 41. Eto, M., and Brautigan*, D. L. (2007) Assay for 3-way interaction of protein phosphatase-1 (Glu7) with regulatory subunits plus phosphatase inhibitor-2. Meth Mol Biol, in press.
- 42. Dimopoulous, G. J., Semba, S., Kitazawa, K., Eto, M., and Kitazawa, T., (2007) Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle. Circ. Res., 100, 121-129. Highlighted in "Editorials" of the Journal.
- 43. Eto, M., Kirkbride, J., Elliott, E., Lo, S. H., and Brautigan*, D. L., (2007) Association of the tensin N-terminal PTP domain with alpha isoform of protein phosphatase-1 in focal adhesions. J. Biol. Chem, 282, 17806-17815.
- 44. Eto*, M., Kitazawa, T., Matsuzawa, F., Aikawa, S., Kirkbride, J. A., Isozumi, N., Nishikawa, Y., Brautigan, D. L., and Ohki, S. (2007) Phosphorylation-induced conformational switching of CPI-17 produces a potent myosin phosphatase inhibitor. Structure,15, 1591-1602.
- 45. Freitas, M. R., Eto*, M., Kirkbride, J. A., Schott, C., Sassard, J., and Stoclet, J. C. (2009) Y27632, a Rho-activated kinase inhibitor, normalizes dysfunction in alpha1-adrenergic receptor-induced contraction of Lyon hypertension rat artery smooth muscle. Fund. Clin. Pharm. 23, 169-178, PMID 19298234.
- 46. Neppl, R. L., Lubomirov, L. T., Momotani, K., Pfitzer, G., Eto, M., and Somlyo*, A. V. (2009) Thromboxan A2-induced bi-directional regulation of serebral arterial tone. J. Biol. Chem., 284, 6348-6360, PMID 19095646.
- 47. Kim, J. I., Young, G. D., Jin, L., Somlyo, A. V., and Eto*, M. (2009) Expression of CPI-17 in smooth muscle during embryonic development and in neointimal lesion formation. Histochem. Cell Biol. 132, 191-198.
- 48. Kitazawa*, T., Semba, S., Huh, Y. H., Kitazawa, K., and Eto, M. (2009) Nitric oxide-induced biphasic mechanism of vascular relaxation via dephosphorylation of CPI-17 and MYPT1. J. Physiol. 587, 3587-3603. Highlighted in "perspectives" of the Journal
- 49. Choudhury, N., Stevenson, A. S., Somlyo, A. V., and Eto*, M. (2009) Phosphorylation-dependent autoinhibition of myosin phosphatase controls Ca2+-sensitivity of smooth muscle contraction. J. Biol. Chem., 284, 21569-21579.
- 50. Xiao, L., Eto, M., and Kazanietz*, M. G. (2009) ROCK mediates phorbol ester-induced apoptosis in prostate cancer cells via p21CIP up-regulation and JNK. J. Biol. Chem., Accepted for publication
- 51. Mori, S., Iwaoka, R., Eto, M., and Ohki*, S. (2009) Solution structure of the inhibitory phosphorylation domain of myosin phosphatase targeting subunit 1. Proteins, Accepted for publication
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- Other Breakthrough Publications (before 2004)
- Eto, M., Ohmori, T., Suzuki, M., Furuya, K. and Morita*, F. (1995) A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization. J. Biochem. 118: 1104-1107.
- Eto, M., Senba, S., Morita, F. and Yazawa*, M. (1997) Molecular cloning of a novel Phosphorylation-dependent inhibitory protein of protein phosphatase-1 (CPI17) in smooth muscle. FEBS Lett. 410: 356-360. Discovery of CPI-17
- Kitazawa*, T., Takizawa, N., Ikebe, M. and Eto, M. (1999) Reconstitution of protein kinase C-induced contractile Ca2+ sensitization in Triton X-100-demembraned rabbit arterial smooth muscle. J. Physiol.(London) 520: 139-152. Highlighted in "Perspectives" of the Journal.
- Eto, M., Karginov, A. and Brautigan*, D. L. (1999) A novel phosphoprotein inhibitor of protein type-1 phosphatase holoenzyme. Biochemistry 38: 16952-16957 Discovery of PHI-1
- Kitazawa*, T., Eto, M., Woodsome, T. P. and Brautigan, D. L. (2000) Agonists trigger G protein-mediated activation of CPI-17 inhibitor phosphoprotein of myosin light chain phosphatase to enhance vascular smooth muscle contractility. J. Biol. Chem. 275: 9897-9900.
- Eto, M., Wong, L., Yazawa, M. and Brautigan, D. L. (2000) Inhibition of myosin/moesin phosphatase by expression of the phosphoinhibitor protein CPI-17 alters microfilament organization and retards cell spreading. Cell Motil.Cytoskel. 46: 222-234. Contributed image for journal cover.
- Ohki, S., Eto, M., Kariya, E., Hayano, T., Hayashi, Y., Yazawa, M., Brautigan, D. L. and Kainosho, M. (2001) Solution NMR structure of the myosin phosphatase inhibitor protein CPI-17 shows phosphorylation-induced conformational changes responsible for activation. J. Mol. Biol. 314: 839-849.
- Eto, M., Bock, R., Brautigan, D. L. and Linden*, D. J. (2002) Cerebellar long-term synaptic depression requires protein-kinase-C mediated inhibition of CPI-17, a myosin/moesin phosphatase inhibitor. Neuron, 36, 1145-1158.
- Eto, M., Kitazawa, T., and Brautigan, D. L. (2004) Phosphoprotein inhibitor CPI-17 specificity depends on allosteric regulation of the protein phosphatase-1 catalytic subunit by regulatory subunits. Proc. Natl. Acad. Sci. USA. 101, 8888-8893. (Track II, direct submission)
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- Review Articles
- 1. Ohki, S., Eto, M., Matsuzawa, F., and Kainosho, M. (2005) Structural basis of a myosin phosphatase inhibitory protein, CPI-17. Seibutsu Butsuri, 45 (2) 72-77
- 2. Eto, M., and Yazawa, M. (2005) Function and regulation of Ser/Thr-specific protein phosphatase-1 (PP1). Seikagaku, 77 (10), 1308-1316
- 3. Eto, M. (2008) Mechanism underlying myosin phosphatase regulation. Vascular Biology and Medicine, 9 (3), 213-221
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Individual Expertise profile of
Masumi Eto, Ph.D., Copyright © Masumi Eto, Ph.D..
Last Updated
by Masumi Eto, Ph.D. : Monday, August 24, 2009 9:30:58 AM
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