2.50
Hdl Handle:
http://hdl.handle.net/10033/279060
Title:
Protein Kinase Inhibitors CK59 and CID755673 Alter Primary Human NK Cell Effector Functions.
Authors:
Scheiter, Maxi; Bulitta, Björn; van Ham, Marco; Klawonn, Frank; König, Sebastian; Jänsch, Lothar ( 0000-0002-5655-1181 )
Abstract:
Natural killer (NK) cells are part of the innate immune response and play a crucial role in the defense against tumors and virus-infected cells. Their effector functions include the specific killing of target cells, as well as the modulation of other immune cells by cytokine release. Kinases constitute a relevant part in signaling, are prime targets in drug research and the protein kinase inhibitor Dasatinib is already used for immune-modulatory therapies. In this study, we tested the effects of the kinase inhibitors CK59 and CID755673. These inhibitors are directed against calmodulin kinase II (CaMKII; CK59) and PKD family kinases (CID755673) that were previously suggested as novel components of NK activation pathways. Here, we use a multi-parameter, FACS-based assay to validate the influence of CK59 and CID755673 on the effector functions of primary NK cells. Treatment with CK59 and CID755673 indeed resulted in a significant dose-dependent reduction of NK cell degranulation markers and cytokine release in freshly isolated Peripheral blood mononuclear cell populations from healthy blood donors. These results underline the importance of CaMKII for NK cell signaling and suggest protein kinase D2 as a novel signaling component in NK cell activation. Notably, kinase inhibition studies on pure NK cell populations indicate significant donor variations.
Affiliation:
Research Group Cellular Proteomics, Helmholtz Centre for Infection Research Braunschweig, Germany.
Citation:
Protein Kinase Inhibitors CK59 and CID755673 Alter Primary Human NK Cell Effector Functions. 2013, 4:66 Front Immunol
Journal:
Frontiers in immunology
Issue Date:
2013
URI:
http://hdl.handle.net/10033/279060
DOI:
10.3389/fimmu.2013.00066
PubMed ID:
23508354
Type:
Article
Language:
en
ISSN:
1664-3224
Appears in Collections:
publications of the research group cellular proteom research (CPRO)

Full metadata record

DC FieldValue Language
dc.contributor.authorScheiter, Maxien_GB
dc.contributor.authorBulitta, Björnen_GB
dc.contributor.authorvan Ham, Marcoen_GB
dc.contributor.authorKlawonn, Franken_GB
dc.contributor.authorKönig, Sebastianen_GB
dc.contributor.authorJänsch, Lotharen_GB
dc.date.accessioned2013-04-05T09:00:06Zen
dc.date.available2013-04-05T09:00:06Zen
dc.date.issued2013en
dc.identifier.citationProtein Kinase Inhibitors CK59 and CID755673 Alter Primary Human NK Cell Effector Functions. 2013, 4:66 Front Immunolen_GB
dc.identifier.issn1664-3224en
dc.identifier.pmid23508354en
dc.identifier.doi10.3389/fimmu.2013.00066en
dc.identifier.urihttp://hdl.handle.net/10033/279060en
dc.description.abstractNatural killer (NK) cells are part of the innate immune response and play a crucial role in the defense against tumors and virus-infected cells. Their effector functions include the specific killing of target cells, as well as the modulation of other immune cells by cytokine release. Kinases constitute a relevant part in signaling, are prime targets in drug research and the protein kinase inhibitor Dasatinib is already used for immune-modulatory therapies. In this study, we tested the effects of the kinase inhibitors CK59 and CID755673. These inhibitors are directed against calmodulin kinase II (CaMKII; CK59) and PKD family kinases (CID755673) that were previously suggested as novel components of NK activation pathways. Here, we use a multi-parameter, FACS-based assay to validate the influence of CK59 and CID755673 on the effector functions of primary NK cells. Treatment with CK59 and CID755673 indeed resulted in a significant dose-dependent reduction of NK cell degranulation markers and cytokine release in freshly isolated Peripheral blood mononuclear cell populations from healthy blood donors. These results underline the importance of CaMKII for NK cell signaling and suggest protein kinase D2 as a novel signaling component in NK cell activation. Notably, kinase inhibition studies on pure NK cell populations indicate significant donor variations.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Frontiers in immunologyen_GB
dc.titleProtein Kinase Inhibitors CK59 and CID755673 Alter Primary Human NK Cell Effector Functions.en
dc.typeArticleen
dc.contributor.departmentResearch Group Cellular Proteomics, Helmholtz Centre for Infection Research Braunschweig, Germany.en_GB
dc.identifier.journalFrontiers in immunologyen_GB

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