Masumi Eto, PhD
Philadelphia, PA 19107
(215) 503-2073 fax
Research & Clinical Interests
PHOSPHATASE SIGNALING IN REGULATION OF CELL MOTILITY
The long-term goal of our research is to understand signal transduction controlling cell motility, a fundamental process for every aspect in biology. Environmental cues, such as released chemical substances and physical stresses, trigger reorganization of cytoskeletons, resulting in force generation, morphological change, transportation, and migration. Signals controlling cell motility are dynamic and orchestrated in TIME and SPACE. Not surprisingly, dysfunctions in the cytoskeletal reorganization have been linked to various diseases, as well as served as a therapeutic target to normalize pathological situations.
Our research focus involves roles of protein phosphatases in the regulation of cell motility. For example, smooth muscle contraction is controlled through the phosphorylation of myosin, a motor protein. Agonist stimulation activates G-proteins, resulting in an enhance in kinase in parallel to the inhibition of phosphatase. The inhibition of phosphatase is necessary for robust and sustained myosin phosphorylation and force generation. In general, multiple regulatory elements are involved in cellular phosphatase regulation, while a limited knowledge of the mechanisms controlling phosphatase activity is currently available.
We use a multidisciplinary approach, including techniques in biochemistry, cell biology, structural biology and physiology, to understand spatio-temporal regulation of cell motility via phosphatases. Our works uncovered a novel family of endogenous phosphatase inhibitor proteins that mediate kinase signal into phosphatase. These are highlights of our research:
- Understanding of spatio-temporal regulation of protein phosphatases that control cell motility, neuronal transmission, cancer cell migration and cytokinesis.
FASEB J. 2003, J Biol. Chem. 2001, 2002, 2007, Neuron 2002, J Cell Sci. 2002, 2006, Cell Motil. Cytoskel. 2000, 2005
- Characterization of signal transduction controlling agonist-induced smooth muscle contraction and relaxation.
J. Biol. Chem. 2000, 2001, 2009, Circ. Res. 2007, J. Physiol. 2009
- Structural sights into regulation of protein phosphatases.
J Mol Biol 2001, 2002, PNAS 2003, Structure 2007
Most Recent Peer-Reviewed Publications
- Protein phosphatases 1 and 2A and their naturally occurring inhibitors: current topics in smooth muscle physiology and chemical biology
- Unfair competition governs the interaction of pCPI-17 with myosin phosphatase (PP1-MYPT1)
- Diversity and plasticity in signaling pathways that regulate smooth muscle responsiveness: Paradigms and paradoxes for the myosin phosphatase, the master regulator of smooth muscle contraction
- F-actin clustering and cell dysmotility induced by the pathological W148R missense mutation of filamin B at the actin-binding domain
- Reconstituted human myosin light chain phosphatase reveals distinct roles of two inhibitory phosphorylation sites of the regulatory subunit, MYPT1
- Nuclear localization of CPI-17, a protein phosphatase-1 inhibitor protein, affects histone H3 phosphorylation and corresponds to proliferation of cancer and smooth muscle cells
- Endogenous inhibitor proteins that connect Ser/Thr kinases and phosphatases in cell signaling
- Caffeine relaxes smooth muscle through actin depolymerization
- Reciprocal regulation controlling the expression of CPI-17, a specific inhibitor protein for the myosin light chain phosphatase in vascular smooth muscle cells
- Molecular mechanism of telokin-mediated disinhibition of myosin light chain phosphatase and cAMP/cGMP-induced relaxation of gastrointestinal smooth muscle
- Interleukin 6 mediates production of interleukin 10 in metastatic melanoma
- Effects of a fluorescent myosin light chain phosphatase inhibitor on prostate cancer cells
- Heat shock augments angiotensin II-induced vascular contraction through increased production of reactive oxygen species
- Regulation of cellular protein phosphatase-1 (PP1) by phosphorylation of the CPI-17 family, C-kinase-activated PP1 Inhibitors
- Solution structure of the inhibitory phosphorylation domain of myosin phosphatase targeting subunit 1
- ROCK mediates phorbol ester-induced apoptosis in prostate cancer cells via p21 Cip1 up-regulation and JNK
- Phosphorylation-dependent autoinhibition of myosin light chain phosphatase accounts for Ca2+ sensitization force of smooth muscle contraction
- Expression of CPI-17 in smooth muscle during embryonic development and in neointimal lesion formation
- Nitric oxide-induced biphasic mechanism of vascular relaxation via dephosphorylation of CPI-17 and MYPT1
- Y27632, a Rho-activated kinase inhibitor, normalizes dysregulation in alpha1-adrenergic receptor-induced contraction of Lyon hypertensive rat artery smooth muscle