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J. Biochem, 2003, Vol. 134, No. 3 327-331
© 2003 Japanese Biochemical Society


JB MINIREVIEWS

Structural Basis of the Rho GTPase Signaling

Toshio Hakoshima*,1,2, Toshiyuki Shimizu3 and Ryoko Maesaki1,4

1 Structural Biology Laboratory, Nara Institute of Science and Technology, and 2 CREST, Japan Science and Technology Corporation, 8916-5 Takayama, Ikoma, Nara 630-0192; 3 Science of Biological Supramolecular Systems, Yokohama-city University, 1-7-29 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa 230-0045; and 4 Research fellow of the Japan Society for the Promotion of Science

ABSTRACT

Small GTPases of the Rho family serve as conformational switches in a wide variety of signal transduction pathways that regulate diverse cellular functions. The GTP-bound forms of Rho GTPases are capable of interacting with downstream effectors that control cytoskeletal rearrangements. Regulators that stimulate nucleotide exchange, the hydrolytic cycle and distribution between the membrane and cytosol control the switch. Detailed pictures of Rho GTPase switching, effector recognition and regulation by regulators have emerged from recent structural investigations. These include the most extensively studied Rho GTPases, RhoA, Rac1, 2 and Cdc42, and their complexes with effectors and regulators. These studies have revealed the general diversity of effector and regulator structures, and in particular the structural features concerning the specific interactions involved in Rho effector recognition and regulator interactions with Rho GTPase. These findings provide a critical insight into the nature of Rho GTPase activity and consequently allow for a detailed manipulation of signaling pathways mediated by these proteins.

FOOTNOTES

* To whom correspondence should be addressed. Tel: +81-743-72-5570, Fax: +81-743-72-5579, E-mail: hakosima{at}bs.aist-nara.ac.jp


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