Department of Cell Biology & Molecular Medicine
Junichi Sadoshima, Ph.D., M.D.
Ph.D., 1992, Kyushu University Faculty of Medicine
M.D., 1983, Kyushu University Faculty of Medicine
|Kim TG, Chen J, Sadoshima J, Lee Y Jumonji represses atrial natriuretic factor gene expression by inhibiting transcriptional activities of cardiac transcription factors. Mol Cell Biol In press 2004.|
|Hardt SE, Tomita H, Katus HA, Sadoshima J. Phosphorylation of eIF2Be by glycogen synthase kinase-3b regulates b-adrenergic cardiac myocyte hypertrophy. Circ Res 94, 926 ? 935, 2004.|
|Yamamoto M, Yang G, Hong C, Liu J, Holle E, Yu X, Wagner T, Vatner SF, Sadoshima J. Inhibition of thioredoxin in the heart increases oxidative stress and cardiac hypertrophy. J Clin Invest. 112, 1395-1406, 2003.|
|Tomita H, Nazmy M, Kajimoto K, Yehia G, Molina CA, Sadoshima J. Inducible cAMP early repressor (ICER) is a negative feedback regulator of cardiac hypertrophy and an important mediator of cardiac myocyte apoptosis in response to b-adrenergic receptor stimulation. Circ Res 93, 12-22, 2003.|
|Yamamoto S, Yang G, Zablocki D, Liu J, Hong C, Kim S-J, Soler S, Odashima M, Thaisz J, Yehia G, Molina CA, Yatani A, Vatner DE, Vatner SF and Sadoshima J. Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy. J Clin Invest. 111, 1463-1474, 2003.|
|Seta K, Sadoshima J Phosphorylation of tyrosine 319 of the AT1 receptor mediates angiotensin II-induced trans-activation of the EGF receptor. J Biol Chem, 278, 9019-9026, 2003.|
|Sadoshima J, Montagne O, Wang Q, Yang G, Warden J, Liu, J, Takagi G, Karoor V, Hong C, Johnson GL, Vatner DE, Vatner SF The MEKK1-JNK pathway plays a protective role in pressure overload but does not mediate cardiac hypertrophy. J Clin Invest. 110, 271-279, 2002.|
|Seta K, Nanamori M, Modrall JG, Neubig RR, Sadoshima J AT1 receptor mutant lacking heterotrimeric G protein coupling activates the Src-Ras-ERK pathway without nuclear translocation of ERKs. J Biol Chem: 277, 9268-9277, 2002.|
|Morisco C, Seta K, Lee Y, Vatner, SF, Sadoshima J Akt/GSK3b regulates GATA4 in cardiac myocytes J Biol Chem: 276, 28586-28597, 2001.|
|Morisco C, Zebrowski DC, Vatner SF, Sadoshima J. The Akt-GSK3b pathway r regulates transcription of ANF induced by b adrenergic receptor stimulation in cardiac myocytes. J. Biol. Chem.: 275, 14466-14475, 2000.|
Areas of Interest
The role of Mst1 in cardiac myocyte apoptosis
Mammalian-sterile 20 like kinase (Mst1) is an important mediator of apoptosis. A Drosophila homologue of Mst1 not only stimulates apoptosis but also inhibits cell cycle progression. Mammalian downstream targets of Mst1 are being investigated.
The role of Sir2 in cardiac myocyte aging and stress resistance
Sir2 is a class III histone deacetylase and an evolutionarily conserved longevity factor. Sir2 deacetylates various transcription factors, including p53 and FOXO, thereby regulating growth and death of many cell types. In vivo function of Sir2 alpha is being investigated using transgenic mice.
Negative regulators of cardiac hypertrophy
In vivo function of endogenous inhibitors of cardiac hypertrophy, including glycogen synthase kinase 3, thioredoxin, tubular sclerosis complex, inducible cyclic AMP early repressor are being investigated using transgenic as well as gene targeting approaches.
The role of thioredoxin in growth and death of cardiac myocytes
Thioredoxin is a 12 kD anti-oxidant having versatile functions. It works as a secreted growth factor, regulates activities of intracellular signaling molecules through direct interaction, and controls transcription. Downstream targets of thioredoxin are being searched using genomic and proteomic approaches.
G-protein independent signaling mechanisms of the heterotrimeric G protein coupled receptors (GPCRs)
Recent evidence suggests that GPCRs have heterotrimeric G protein-independent functions, such as the one through direct protein-protein interaction. Using angiotensin II receptor mutants lacking heterotrimeric G protein coupling, G-protein independent functions of the GPCRs are being investigated.