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Laboratory of Cell Regulation |
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Signal Transduction Group
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Kunihiro Matsumoto Professor
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Kunihiro Matsumoto (Professor)
Signal transduction networks regulating the development
and differentiation of organisms
Naoki Hisamoto (Associate Professor)
Signal transduction networks in entire organisms using
nematode as a model animal
Hiroshi Hanafusa (Assistant Professor)
Signal transduction networks involved in axis
formation in early Xenopus embryos
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Studies of signal transduction networks have provided important
insights for our understanding of the regulation of various cellular
events, including cell proliferation, differentiation, stress responses,
and behavior. Signal transduction pathways detect extracellular signals
at the cell surface and transmit them through the cytoplasm to nuclear
and other intracellular targets. The mechanisms of intracellular signal
transmission involve players that are conserved in organisms as diverse
as nematodes and humans. In our laboratory, we are investigating the
molecular mechanisms of signal transduction networks that control
various biological regulatory systems in Caenorhabditis elegans
(nematode), Xenopus laevis (frog) and Mus musculus (mouse).
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Signal transduction cascades in C. elegans as a model animal
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| Fig1. Regulation of neuronal left-right asymmetry
by SEK-1 |
The nematode C. elegans is an animal of 1-2 mm length that
feeds on bacteria in soil. Recently, C. elegans has been highlighted
as a model multicellular organism because it has many genes that have
homologues in mammals. In addition, C. elegans is useful for
genetic and molecular biological analysis. In our laboratory, we focus
on clarifying the mechanisms of neural function, development, differentiation,
immunity, stress response, and hereditary disease by functional analysis
of the signal transduction networks conserved between nematodes and
humans. We have reported on the roles of signal transduction pathways
in the control of nervous function, cell fate decision, innate immunity,
and early development. Further analysis will elucidate the precise
mechanisms by which signal transduction pathways control various cellular
events.
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Molecular mechanisms of signal transduction during early Xenopus
development
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Xenopus laevis is a very useful organism for studying early development. In particular, we are focused on isolating new genes that are involved in mesoderm formation or neural formation. To date, we have successfully identified several candidate genes. Neural tissues are formed by the interactions of several signaling pathways (FGF signaling, Wnt signaling, BMP signaling, and others). Based on findings in early Xenopus embryogenesis, we will elucidate the existence
of conserved mechanisms in higher eukaryotes using mammalian ES cells.
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Signal transduction cascades involving TAK1 (MAPKKK) in mammalian
cells
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| Fig2. TAK1 signal transduction cascades |
TAK1 is a member of the MAP kinase kinase kinase (MAPKKK) family isolated
in our laboratory. We found that TAK1 executes many important roles
in various signal transduction pathways. These include the TGFβ-
pathway, which regulates morphogenesis and cell growth, the interleukin-1
(IL-1) pathway, which regulates immune responses, and the Wnt pathway,
which regulates cell fate decisions during development.
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| Members of signal transduction group |
We are trying to
clarify the mechanisms by which TAK1 is regulated by various signals
and how these signals regulate specific cellular events.
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References
- Ishitani, T. et al. (2005) Nature Cell Biol. 11:
1106.
- Nishiwaki, K. et al. (2004) Nature Cell Biol.
6: 31.
- McGuire, S.E. et al. (2003) Science 302: 1754.
- Kim, D.H. et al. (2002) Science 297: 623.
- Kondo, T. et al. (2001) Science 294: 86.
- Nishiwaki, K. et al. (2000) Science 288: 2205.
- Ninomiya-Tsuji, J. et al. (1999) Nature 398: 252.
- Meneghini, M.D. et al. (1999) Nature 399: 793.
- Ishitani, T. et al. (1999) Nature 399: 798.
- Adachi-Yamada, T. et al. (1999) Nature 400: 166.
- Kurokawa, M. et al. (1998) Nature 394: 92.
- Ichijo, H. et al. (1997) Science 275: 90.
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i n d e x |
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 Signal
Transduction Group
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Molecular
Neurobiology Group