JNK MAP kinase activation is required for MTOC and granule polarization in NKG2D-mediated NK cell cytotoxicity.
Proc Natl Acad Sci U S A
; 105(8): 3017-22, 2008 Feb 26.
Article
em En
| MEDLINE
| ID: mdl-18287025
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 inhibitors of Src protein tyrosine kinases and phospholipase PLCgamma, upstream of JNK. Similarly, a second MAP kinase pathway through ERK was previously shown to be required for NK cell cytotoxicity. Thus, activation of two MAP kinase pathways is required for cytotoxic granule and MTOC polarization and for cytotoxicity of human NK cells when NKG2D is ligated.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Receptores Imunológicos
/
Transdução de Sinais
/
Polaridade Celular
/
Proteínas Quinases JNK Ativadas por Mitógeno
Limite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos