Protein Kinase Inhibitors CK59 and CID755673 Alter Primary Human NK Cell Effector Functions.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
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.
CitationProtein Kinase Inhibitors CK59 and CID755673 Alter Primary Human NK Cell Effector Functions. 2013, 4:66 Front Immunol
AffiliationResearch Group Cellular Proteomics, Helmholtz Centre for Infection Research Braunschweig, Germany.
JournalFrontiers in immunology
The following license files are associated with this item:
- Nonspecific, reversible inhibition of voltage-gated calcium channels by CaMKII inhibitor CK59.
- Authors: Karls AS, Mynlieff M
- Issue date: 2013 Jul
- Enhancement of natural killer cell effector functions against selected lymphoma and leukemia cell lines by dasatinib.
- Authors: Hassold N, Seystahl K, Kempf K, Urlaub D, Zekl M, Einsele H, Watzl C, Wischhusen J, Seggewiss-Bernhardt R
- Issue date: 2012 Sep 15
- Potent and selective disruption of protein kinase D functionality by a benzoxoloazepinolone.
- Authors: Sharlow ER, Giridhar KV, LaValle CR, Chen J, Leimgruber S, Barrett R, Bravo-Altamirano K, Wipf P, Lazo JS, Wang QJ
- Issue date: 2008 Nov 28
- NK-cell-dependent killing of colon carcinoma cells is mediated by natural cytotoxicity receptors (NCRs) and stimulated by parvovirus infection of target cells.
- Authors: Bhat R, Rommelaere J
- Issue date: 2013 Jul 31
- Preparation and use of HIV-1 infected primary CD4+ T-cells as target cells in natural killer cell cytotoxic assays.
- Authors: Davis ZB, Ward JP, Barker E
- Issue date: 2011 Mar 14