dc.contributor.authorJain, Neeraj
dc.contributor.authorTan, Jun Hou
dc.contributor.authorFeng, Shijin
dc.contributor.authorGeorge, Bhawana
dc.contributor.authorThanabalu, Thirumaran
dc.date.accessioned2014-11-10T09:04:00Z
dc.date.available2014-11-10T09:04:00Z
dc.date.copyright2014en_US
dc.date.issued2014
dc.identifier.citationJain, N., Tan, J. H., Feng, S., George, B., & Thanabalu, T. (2014). X-Linked thrombocytopenia causing mutations in WASP (L46P and A47D) impair T cell chemotaxis. Journal of biomedical science, 21(1), 91-.en_US
dc.identifier.issn1423-0127en_US
dc.identifier.urihttp://hdl.handle.net/10220/24212
dc.description.abstractBackground: Mutation in the Wiskott-Aldrich syndrome Protein (WASP) causes Wiskott-Aldrich syndrome (WAS), X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN). The majority of missense mutations causing WAS and XLT are found in the WH1 (WASP Homology) domain of WASP, known to mediate interaction with WIP (WASP Interacting Protein) and CIB1 (Calcium and Integrin Binding). Results: We analyzed two WASP missense mutants (L46P and A47D) causing XLT for their effects on T cell chemotaxis. Both mutants, WASPRL46P and WASPRA47D (S1-WASP shRNA resistant) expressed well in JurkatWASP-KD T cells (WASP knockdown), however expression of these two mutants did not rescue the chemotaxis defect of JurkatWASP-KD T cells towards SDF-1α. In addition JurkatWASP-KD T cells expressing these two WASP mutants were found to be defective in T cell polarization when stimulated with SDF-1α. WASP exists in a closed conformation in the presence of WIP, however both the mutants (WASPRL46P and WASPRA47D) were found to be in an open conformation as determined in the bi-molecular complementation assay. WASP protein undergoes proteolysis upon phosphorylation and this turnover of WASP is critical for T cell migration. Both the WASP mutants were found to be stable and have reduced tyrosine phosphorylation after stimulation with SDF-1α. Conclusion: Thus our data suggest that missense mutations WASPRL46P or WASPRA47D affect the activity of WASP in T cell chemotaxis probably by affecting the turnover of the protein.en_US
dc.format.extent12 p.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesJournal of biomedical scienceen_US
dc.rights© 2014 Jain et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en_US
dc.subjectDRNTU::Science::Biological sciences
dc.titleX-Linked thrombocytopenia causing mutations in WASP (L46P and A47D) impair T cell chemotaxisen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.identifier.doihttp://dx.doi.org/10.1186/s12929-014-0091-1
dc.description.versionPublished versionen_US


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