3ryt
From Proteopedia
The Plexin A1 intracellular region in complex with Rac1
Structural highlights
Function[PLXA1_MOUSE] Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.[1] [2] [RAC1_HUMAN] Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion.[3] [4] [5] [6] [7] Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.[8] [9] [10] [11] [12] Publication Abstract from PubMedPlexins 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. Plexins Are GTPase-Activating Proteins for Rap and Are Activated by Induced Dimerization.,Wang Y, He H, Srivastava N, Vikarunnessa S, Chen YB, Jiang J, Cowan CW, Zhang X Sci Signal. 2012 Jan 17;5(207):ra6. PMID:22253263[13] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Mus musculus | He, H | Zhang, X | Gtpase activating protein | Plexin | Rac | Rasgap | Signaling protein
