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dc.contributor.authorMCLOUGHLIN, DECLAN
dc.date.accessioned2009-11-12T13:49:35Z
dc.date.available2009-11-12T13:49:35Z
dc.date.issued2005
dc.date.submitted2005en
dc.identifier.citationTudor, EL, Perkinton, MS, Schmidt, A, Ackerley, S, Brownlees, J, Jacobsen, NJ, Byers, HL, Ward, M, Hall, A, Leigh, PN, Shaw, CE, McLoughlin, DM, Miller, CC, `ALS2/Alsin regulates Rac-PAK signaling and neurite outgrowth? in The Journal of Biological Chemistry, 280, (41), 2005, pp 34735 - 34740en
dc.identifier.otherY
dc.identifier.other55892
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/34666
dc.descriptionPUBLISHEDen
dc.description.abstractRac and its downstream effectors p21-activated kinase (PAK) family kinases regulate actin dynamics within growth cones to control neurite outgrowth during development. The activity of Rac is stimulated by guanine nucleotide exchange factors (GEFs) that promote GDP release and GTP binding. ALS2/Alsin is a recently described GEF that contains a central domain that is predicted to regulate the activities of Rac and/or Rho and Cdc42 activities. Mutations in ALS2 cause some recessive familial forms of amyotrophic lateral sclerosis (ALS) but the function of ALS2 is poorly understood. Here we demonstrate that ALS2 is present within growth cones of neurons, in which it co-localizes with Rac. Furthermore, ALS2 stimulates Rac but not Rho or Cdc42 activities, and this induces a corresponding increase in PAK1 activity. Finally, we demonstrate that ALS2 promotes neurite outgrowth. Defects in these functions may therefore contribute to motor neuron demise in ALS.en
dc.description.sponsorshipThis work was supported by grants from the Medical Research Council and Wellcome Trust (to C. C. J. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked ?advertisement? in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.en
dc.format.extent34735en
dc.format.extent34740en
dc.format.extent582794 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.relation.ispartofseriesThe Journal of Biological Chemistryen
dc.relation.ispartofseries280en
dc.relation.ispartofseries41en
dc.rightsYen
dc.subjectPsychiatryen
dc.titleALS2/Alsin regulates Rac-PAK signaling and neurite outgrowth.en
dc.typeJournal Articleen
dc.contributor.sponsorMedical Research Council
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mclougde
dc.identifier.rssurihttp://dx.doi.org/10.1074/jbc.M506216200


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