File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1084/jem.186.6.941
- Scopus: eid_2-s2.0-0030931125
- PMID: 9294148
- WOS: WOS:A1997XX67800015
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes
Title | Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes |
---|---|
Authors | |
Issue Date | 1997 |
Citation | Journal of Experimental Medicine, 1997, v. 186, n. 6, p. 941-953 How to Cite? |
Abstract | The dual specific kinase SAPK/ERK1 kinase (SEK1; mitogen-activated protein kinase kinase 4/Jun NH 2 terminal kinase [JNK] kinase) is a direct activator of stress-activated protein kinases ([SAPKs]/JNKs) in response to CD28 costimulation, CD40 signaling, or activation of the germinal center kinase. Here we show that SEK1(-/-) recombination-activating gene (RAG)2(-/- ) chimeric mice have a partial block in B cell maturation. However, peripheral B cells displayed normal responses to IL-4, IgM, and CD40 cross- linking. SEK1(-/-) peripheral T cells showed decreased proliferation and IL- 2 production after CD28 costimulation and PMA/Ca 2+ ionophore activation. Although CD28 expression was absolutely crucial to generate vesicular stomatitis virus (VSV)-specific germinal centers, SEK1(-/-)RAG2(-/-) chimeras mounted a protective antiviral B cell response, exhibited normal IgG class switching, and made germinal centers in response to VSV. Interestingly, PMA/Ca 2+ ionophore stimulation, which mimics TCR-CD3 and CD28-mediated signal transduction, induced SAPK/JNK activation in peripheral T cells, but not in thymocytes, from SEK1(-/-) mice. These results show that signaling pathways for SAPK activation are developmentally regulated in T cells. Although SEK1(-/-) thymocytes failed to induce SAPK/JNK in response to PMA/Ca 2+ ionophore, SEK1(-/-)RAG2(-/-) thymocytes proliferated and made IL- 2 after PMA/Ca 2+ ionophore and CD3/CD28 stimulation, albeit at significantly lower levels compared to SEK1(+/+)RAG2(-/-) thymocytes, implying that CD28 costimulation and PMA/Ca 2+ ionophore-triggered signaling pathways exist that can mediate proliferation and IL-2 production independently of SAPK activation. Our data provide the first genetic evidence that SEK1 is an important effector molecule that relays CD28 signaling to IL- 2 production and T cell proliferation. |
Persistent Identifier | http://hdl.handle.net/10722/291413 |
ISSN | 2023 Impact Factor: 12.6 2023 SCImago Journal Rankings: 6.838 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Nishina, Hiroshi | - |
dc.contributor.author | Bachmann, Martin | - |
dc.contributor.author | Oliveira-dos-Santos, Antonio J. | - |
dc.contributor.author | Kozieradzki, Ivona | - |
dc.contributor.author | Fischer, Klaus D. | - |
dc.contributor.author | Odermatt, Bernhard | - |
dc.contributor.author | Wakeham, Andrew | - |
dc.contributor.author | Shahinian, Arda | - |
dc.contributor.author | Takimoto, Hiroaki | - |
dc.contributor.author | Bernstein, Alan | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Woodgett, James R. | - |
dc.contributor.author | Ohashi, Pamela S. | - |
dc.contributor.author | Penninger, Josef M. | - |
dc.date.accessioned | 2020-11-17T14:54:19Z | - |
dc.date.available | 2020-11-17T14:54:19Z | - |
dc.date.issued | 1997 | - |
dc.identifier.citation | Journal of Experimental Medicine, 1997, v. 186, n. 6, p. 941-953 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | http://hdl.handle.net/10722/291413 | - |
dc.description.abstract | The dual specific kinase SAPK/ERK1 kinase (SEK1; mitogen-activated protein kinase kinase 4/Jun NH 2 terminal kinase [JNK] kinase) is a direct activator of stress-activated protein kinases ([SAPKs]/JNKs) in response to CD28 costimulation, CD40 signaling, or activation of the germinal center kinase. Here we show that SEK1(-/-) recombination-activating gene (RAG)2(-/- ) chimeric mice have a partial block in B cell maturation. However, peripheral B cells displayed normal responses to IL-4, IgM, and CD40 cross- linking. SEK1(-/-) peripheral T cells showed decreased proliferation and IL- 2 production after CD28 costimulation and PMA/Ca 2+ ionophore activation. Although CD28 expression was absolutely crucial to generate vesicular stomatitis virus (VSV)-specific germinal centers, SEK1(-/-)RAG2(-/-) chimeras mounted a protective antiviral B cell response, exhibited normal IgG class switching, and made germinal centers in response to VSV. Interestingly, PMA/Ca 2+ ionophore stimulation, which mimics TCR-CD3 and CD28-mediated signal transduction, induced SAPK/JNK activation in peripheral T cells, but not in thymocytes, from SEK1(-/-) mice. These results show that signaling pathways for SAPK activation are developmentally regulated in T cells. Although SEK1(-/-) thymocytes failed to induce SAPK/JNK in response to PMA/Ca 2+ ionophore, SEK1(-/-)RAG2(-/-) thymocytes proliferated and made IL- 2 after PMA/Ca 2+ ionophore and CD3/CD28 stimulation, albeit at significantly lower levels compared to SEK1(+/+)RAG2(-/-) thymocytes, implying that CD28 costimulation and PMA/Ca 2+ ionophore-triggered signaling pathways exist that can mediate proliferation and IL-2 production independently of SAPK activation. Our data provide the first genetic evidence that SEK1 is an important effector molecule that relays CD28 signaling to IL- 2 production and T cell proliferation. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Experimental Medicine | - |
dc.title | Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1084/jem.186.6.941 | - |
dc.identifier.pmid | 9294148 | - |
dc.identifier.pmcid | PMC2199046 | - |
dc.identifier.scopus | eid_2-s2.0-0030931125 | - |
dc.identifier.volume | 186 | - |
dc.identifier.issue | 6 | - |
dc.identifier.spage | 941 | - |
dc.identifier.epage | 953 | - |
dc.identifier.isi | WOS:A1997XX67800015 | - |
dc.identifier.issnl | 0022-1007 | - |