Laboratories & Administration Office

Laboratory of Intracellular Signaling

member

Director Hiroaki MIKI
Instructor Yousuke FUNATO
Kanami UESUGI

Correspondence

Tel 81-6-6879-8631
Fax 81-6-6879-8633
E-mail
URL http://www.protein.osaka-u.ac.jp/intra_signal/index_e.html

Research

Cells that constitute multicellular organisms are equipped with the signal transduction system, which enables cells to respond appropriately to the surrounding environment such as stimulation with various hormones and growth factors and physical interaction with other cells and matrix. Normal function of this signaling system is essential for cells to play a given function as a single unit in the multicellular society. It is known that malfunction of the signaling system is responsible for various human diseases, which is typically observed in the case of abnormal proliferation of cancer cells. In our laboratory, we are investigating the mechanism of the intracellular signaling that regulates proliferation, differentiation, morphology, and motility of cells, at the level of molecular change, such as post-transcriptional modification and conformational change of functional proteins. Our aim is to artificially control the intracellular signaling based on the precise knowledge on it.


<Fig.1>
Dishevelled (Dvl), a Wnt signal transducing protein, regulates microtubules
and induces neurite extension in neuroblastoma cells (indicated by arrows).


<Fig.2>
Artificial inhibition of expression of NRX, a redox-responsive protein, in
Xenopus results in morphogenetic defects, typically observed as the loss
of eyes (indicated by an arrow).

Current Research Programs

1) Redox-dependent regulation of intracellular signaling
2) Mechanism of signal transduction regulating cell motility and morphology
3) Mechanism of polarity formation/maintenance of axons and dendrites from neurons
4) Mechanism of signal transduction regulating cancer formation

References

1. Nucleoredoxin, a thioredoxin-related redox-regulating protein, inhibits Wnt/β-catenin signaling through Dishevelled. Funato et al. (2006) Nat. Cell Biol. 8, 501-508 .
2. Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin. Yamaguchi et al. (2005) J. Cell Biol. 168, 441-452.
3. WAVE2 is required for directed cell migration and cardiovascular development. Yamazaki et al. (2003) Nature 424, 452-456.
4. IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. Miki et al. (2000) Nature 408, 732-735.

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