Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.25 (triphosphatase)
 1,529 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plexins are cell surface receptors for semaphorin molecules, and their interaction governs cell adhesion and migration in a variety of tissues. We report that the Semaphorin 4D (Sema4D) receptor Plexin-B1 directly stimulates the intrinsic guanosine triphosphatase (GTPase) activity of R-Ras, a member of the Ras superfamily of small GTP-binding proteins that has been implicated in promoting cell adhesion and neurite outgrowth. This activity required the interaction of Plexin-B1 with Rnd1, a small GTP-binding protein of the Rho family. Down-regulation of R-Ras activity by the Plexin-B1-Rnd1 complex was essential for the Sema4D-induced growth cone collapse in hippocampal neurons. Thus, Plexin-B1 mediates Sema4D-induced repulsive axon guidance signaling by acting as a GTPase activating protein for R-Ras.
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PMID:The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras. 1529 73

Plexins are cell surface receptors that bind to semaphorins and transduce signals that regulate neuronal development, immune responses, and other processes. Signaling through plexins has been proposed to rely on specific guanosine triphosphatase (GTPase)-activating protein (GAP) activity for R-Ras and M-Ras. Activation of this GAP activity of plexins appears to require simultaneous binding of semaphorin to the plexin extracellular domain and of the Rho GTPases Rac1 or Rnd1 to the cytoplasmic region. However, GAP activity of plexins has eluded detection in several recent studies. We show that the purified cytoplasmic region of plexin uses a noncanonical catalytic mechanism to act as a GAP for Rap, but not for R-Ras or M-Ras. The RapGAP activity of plexins was autoinhibited and was activated by induced dimerization. Biochemical and crystallographic analyses demonstrated that binding of Rho GTPases did not directly contribute to activation of plexin RapGAP activity. Semaphorin stimulated the RapGAP activity of full-length plexin in cells, which was required for plexin-mediated neuronal growth cone collapse. Together, these findings define a pathway for plexin signaling and provide insights into the mechanism for semaphorin-induced activation of plexins.
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PMID:Plexins are GTPase-activating proteins for Rap and are activated by induced dimerization. 2225 63