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dc.contributor.authorWei, S
dc.contributor.authorGamero, AM
dc.contributor.authorLiu, JH
dc.contributor.authorDaulton, AA
dc.contributor.authorValkov, NI
dc.contributor.authorTrapani, JA
dc.contributor.authorLarner, AC
dc.contributor.authorWeber, MJ
dc.contributor.authorDjeu, JY
dc.date.accessioned2020-12-22T03:43:47Z
dc.date.available2020-12-22T03:43:47Z
dc.date.issued1998-06-01
dc.identifier.citationWei, S., Gamero, A. M., Liu, J. H., Daulton, A. A., Valkov, N. I., Trapani, J. A., Larner, A. C., Weber, M. J. & Djeu, J. Y. (1998). Control of lytic function by mitogen-activated protein kinase extracellular regulatory kinase 2 (ERK2) in a human natural killer cell line: Identification of perforin and granzyme B mobilization by functional ERK2. JOURNAL OF EXPERIMENTAL MEDICINE, 187 (11), pp.1753-1765. https://doi.org/10.1084/jem.187.11.1753.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/257914
dc.description.abstractThe signal pathways that control effector function in human natural killer (NK) cells are little known. In this study, we have identified the critical role of the mitogen-activated protein kinase (MAPK) pathway in NK lysis of tumor cells, and this pathway may involve the mobilization of granule components in NK cells upon interaction with sensitive tumor target cells. Evidence was provided by biological, biochemical, and gene transfection methods. NK cell binding to tumor cells for 5 min was sufficient to maximally activate MAPK/extracellular signal-regulatory kinase 2 (ERK2), demonstrated by its tyrosine phosphorylation and by its ability to function as an efficient kinase for myelin basic protein. MAPK activation was achieved in NK cells only after contact with NK-sensitive but not NK-resistant target cells. In immunocytochemical studies, cytoplasmic perforin and granzyme B were both maximally redirected towards the tumor contact zone within 5 min of NK cell contact with tumor cells. A specific MAPK pathway inhibitor, PD098059, could block not only MAPK activation but also redistribution of perforin/granzyme B in NK cells, which occur upon target ligation. PD098059 also interfered with NK lysis of tumor cells in a 5-h 51Cr-release assay, but had no ability to block NK cell proliferation. Transient transfection studies with wild-type and dominant-negative MAPK/ERK2 genes confirmed the importance of MAPK in NK cell lysis. These results document a pivotal role of MAPK in NK effector function, possibly by its control of movement of lytic granules, and clearly define MAPK involvement in a functional pathway unlinked to cell growth or differentiation.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.titleControl of lytic function by mitogen-activated protein kinase extracellular regulatory kinase 2 (ERK2) in a human natural killer cell line: Identification of perforin and granzyme B mobilization by functional ERK2
dc.typeJournal Article
dc.identifier.doi10.1084/jem.187.11.1753
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.source.titleJournal of Experimental Medicine
melbourne.source.volume187
melbourne.source.issue11
melbourne.source.pages1753-1765
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1179877
melbourne.contributor.authorTrapani, Joseph
dc.identifier.eissn1540-9538
melbourne.accessrightsOpen Access


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