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Title 

RasGRP1 is required for human NK cell function

Authors 

Suk Hyung LeeSohyun YunJi-Won LeeMi-Joung KimZ H PiaoMi-Ra JeongJ W ChungTae-Don KimSuk Ran YoonP D GreenbergIn Pyo Choi

Publisher 

American Association of Immunologists

Issue Date 

2009

Citation 

Journal of Immunology, vol. 183, no. 12, pp. 7931-7938

Abstract 

Cross-linking of NK activating receptors activates phospholipase-gamma and subsequently induces diacylglycerol and Ca(2+) as second messengers of signal transduction. Previous studies reported that Ras guanyl nucleotide-releasing protein (RasGRP) 1, which is activated by diacylglycerol and Ca(2+), 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.

ISSN 

0022-1767

Link 

http://dx.doi.org/10.4049/jimmunol.0902012

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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