Vav regulates peptide-specific apoptosis in thymocytes.
The protooncogene Vav functions as a GDP/GTP exchange factor (GEF) for Rho-like small GTPases involved in cytoskeletal reorganization and cytokine production in T cells. Gene-targeted mice lacking Vav have a severe defect in positive and negative selection of T cell antigen receptor transgenic thymo...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1998
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| _version_ | 1797098340198907904 |
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| author | Kong, Y Fischer, K Bachmann, M Mariathasan, S Kozieradzki, I Nghiem, M Bouchard, D Bernstein, A Ohashi, P Penninger, J |
| author_facet | Kong, Y Fischer, K Bachmann, M Mariathasan, S Kozieradzki, I Nghiem, M Bouchard, D Bernstein, A Ohashi, P Penninger, J |
| author_sort | Kong, Y |
| collection | OXFORD |
| description | The protooncogene Vav functions as a GDP/GTP exchange factor (GEF) for Rho-like small GTPases involved in cytoskeletal reorganization and cytokine production in T cells. Gene-targeted mice lacking Vav have a severe defect in positive and negative selection of T cell antigen receptor transgenic thymocytes in vivo, and vav-/- thymocytes are completely resistant to peptide-specific and anti-CD3/anti-CD28-mediated apoptosis. Vav acts upstream of mitochondrial pore opening and caspase activation. Biochemically, Vav regulates peptide-specific Ca2+ mobilization and actin polymerization. Peptide-specific cell death was blocked both by cytochalasin D inhibition of actin polymerization and by inhibition of protein kinase C (PKC). Activation of PKC with phorbol ester restored peptide-specific apoptosis in vav-/- thymocytes. Vav was found to bind constitutively to PKC-theta in thymocytes. Our results indicate that peptide-triggered thymocyte apoptosis is mediated via Vav activation, changes in the actin cytoskeleton, and subsequent activation of a PKC isoform. |
| first_indexed | 2024-03-07T05:08:06Z |
| format | Journal article |
| id | oxford-uuid:daa1dc5a-9070-4317-a83e-96c49179d259 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:08:06Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:daa1dc5a-9070-4317-a83e-96c49179d2592022-03-27T09:04:32ZVav regulates peptide-specific apoptosis in thymocytes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:daa1dc5a-9070-4317-a83e-96c49179d259EnglishSymplectic Elements at Oxford1998Kong, YFischer, KBachmann, MMariathasan, SKozieradzki, INghiem, MBouchard, DBernstein, AOhashi, PPenninger, JThe protooncogene Vav functions as a GDP/GTP exchange factor (GEF) for Rho-like small GTPases involved in cytoskeletal reorganization and cytokine production in T cells. Gene-targeted mice lacking Vav have a severe defect in positive and negative selection of T cell antigen receptor transgenic thymocytes in vivo, and vav-/- thymocytes are completely resistant to peptide-specific and anti-CD3/anti-CD28-mediated apoptosis. Vav acts upstream of mitochondrial pore opening and caspase activation. Biochemically, Vav regulates peptide-specific Ca2+ mobilization and actin polymerization. Peptide-specific cell death was blocked both by cytochalasin D inhibition of actin polymerization and by inhibition of protein kinase C (PKC). Activation of PKC with phorbol ester restored peptide-specific apoptosis in vav-/- thymocytes. Vav was found to bind constitutively to PKC-theta in thymocytes. Our results indicate that peptide-triggered thymocyte apoptosis is mediated via Vav activation, changes in the actin cytoskeleton, and subsequent activation of a PKC isoform. |
| spellingShingle | Kong, Y Fischer, K Bachmann, M Mariathasan, S Kozieradzki, I Nghiem, M Bouchard, D Bernstein, A Ohashi, P Penninger, J Vav regulates peptide-specific apoptosis in thymocytes. |
| title | Vav regulates peptide-specific apoptosis in thymocytes. |
| title_full | Vav regulates peptide-specific apoptosis in thymocytes. |
| title_fullStr | Vav regulates peptide-specific apoptosis in thymocytes. |
| title_full_unstemmed | Vav regulates peptide-specific apoptosis in thymocytes. |
| title_short | Vav regulates peptide-specific apoptosis in thymocytes. |
| title_sort | vav regulates peptide specific apoptosis in thymocytes |
| work_keys_str_mv | AT kongy vavregulatespeptidespecificapoptosisinthymocytes AT fischerk vavregulatespeptidespecificapoptosisinthymocytes AT bachmannm vavregulatespeptidespecificapoptosisinthymocytes AT mariathasans vavregulatespeptidespecificapoptosisinthymocytes AT kozieradzkii vavregulatespeptidespecificapoptosisinthymocytes AT nghiemm vavregulatespeptidespecificapoptosisinthymocytes AT bouchardd vavregulatespeptidespecificapoptosisinthymocytes AT bernsteina vavregulatespeptidespecificapoptosisinthymocytes AT ohaship vavregulatespeptidespecificapoptosisinthymocytes AT penningerj vavregulatespeptidespecificapoptosisinthymocytes |