Journal
JOURNAL OF IMMUNOLOGY
Volume 183, Issue 12, Pages 7931-7938Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0902012
Keywords
-
Categories
Funding
- Global Research Laboratory project [FGM 1400913]
- New Drug Target Discovery Project [M10848000352-08N4800-35210]
- Ministry of Education, Science and Technology, Republic of Korea
Ask authors/readers for more resources
Cross-linking of NK activating receptors activates phospholipase-gamma and subsequently induces diacylglycerol and Ca2+ as second messengers of signal transduction. Previous studies reported that Ras guanyl nucleotide-releasing protein (RasGRP) 1, which is activated by diacylglycerol and Ca2+, is crucial for TCR-mediated Ras-ERK activation. We now report that RasGRP1, which can also be detected in human NK cells, plays an essential role in NK cell effector functions. To examine the role of RasGRP1 in NK cell functions, the expression of RasGRP1 was suppressed using RNA interference. Knockdown of RasGRP1 significantly blocked ITAM-dependent cytokine production as well as NK cytotoxicity. Biochemically, RasGRP1-knockdown NK cells showed markedly decreased ability to activate Ras, ERK, and JNK. Activation of the Ras-MAPK pathway was independently shown to be indispensable for NK cell effector functions via the use of specific pharmacological inhibitors. Our results reveal that RasGRP1 is required for the activation of the Ras-MAPK pathway leading to NK cell effector functions. Moreover, our data suggest that RasGRP1 might act as an important bridge between phospholipase-gamma activation and NK cell effector functions via the Ras-MAPK pathway. The Journal of Immunology, 2009, 183: 7931-7938.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available