| Budget Amount *help |
¥15,200,000 (Direct Cost: ¥15,200,000)
Fiscal Year 1998: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1997: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Research Abstract |
The Rho family GTPases (Rho, Cdc42, and Rac) participate in the regulation of cytoskeletons and cell adhesions through their specific targets. However, the molecular mechanisms by which the Rho family GTPases regulate these cellular functions have been largely unknown. Recently, we identified Rho target molecules, Rho-kinase, PKN, and the myosin binding subunit (MBS) of myosin phosphatase, and a Cdc42- and Rac-target IQGAP1. The aim of the present study is to reveal the mechanism how Rho family GTPases and their target proteins regulate cytoskeletons and cell adhesions. Here we found that the cytoskeletal proteins adducin and moesin are in vitro and in vivo substrates of Rho-kinase, the phosphorylations of which modulated cell migration and formation of microvilli-like structures. We also demonstrated that the phosphorylation of myosin light chain by Rho-kinase leads to neurite retraction. In addition, we identified novel Rho-kinase substrate proteins, MAP2, Tau, and CRMP-2. The analysis of the physiological functions of their phosphorylations is on going. As for the Cdc42- and Rac-target IQGAP1, we demonstrated that it negatively regulates cell-cell adhesion by interacting with E-cadherin and beta-caten in. The results obtained here lead us to better understanding how Rho family GTPases regulate cytoskeletons and cell adhesions
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