JNK MAP kinase activation is required for MTOC and granule polarization in NKG2D-mediated NK cell cytotoxicity.

ABSTRACT: Interaction of the activating receptor NKG2D with its ligands is a major stimulatory pathway for cytotoxicity of natural killer (NK) cells. Here, the signaling pathway involved after NKG2D ligation is examined. Either incubation of the NKG2D-bearing human NKL tumor cell line with K562 target cells or cross-linking with NKG2D mAb induced strong activation of the mitogen-activated protein (MAP) kinases. Selective inhibition of JNK MAP kinase with four different means of inhibition greatly reduced NKG2D-mediated cytotoxicity toward target cells and furthermore, blocked the movement of the microtubule organizing center (MTOC), granzyme B (a component of cytotoxic granules), and paxillin (a scaffold protein) to the immune synapse. NKG2D-induced activation of JNK kinase was also blocked by inhib

SUBMITTER: Li C 

PROVIDER: S-EPMC2268577 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature