Structural basis of the Rho GTPase signaling.
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.
Hakoshima
Toshio
T
Structural Biology Laboratory, Nara Institute of Science and Technology, and CREST, Japan Science and Technology Corporation, 8916-5 Takayama, Ikoma, Nara 630-0192. hakosima@bs.aist-nara.ac.jp
Shimizu
Toshiyuki
T
Maesaki
Ryoko
R
D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism
D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; C085379:rho GTPase-activating protein; D020741:rho GTP-Binding Proteins