Ras-related C3 Botulinum Toxin Substrate (Rac) and Src Family Kinases (SFK) Are Proximal and Essential for Phosphatidylinositol 3-Kinase (PI3K) Activation in Natural Killer (NK) Cell-mediated Direct Cytotoxicity against Cryptococcus neoformans.

The Journal of biological chemistry 2016 Vol.291(13) p. 6912-22

Xiang RF, Stack D, Huston SM, Li SS, Ogbomo H, Kyei SK, Mody CH

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Abstract

The activity of Rac in leukocytes is essential for immunity. However, its role in NK cell-mediated anti-microbial signaling remains unclear. In this study, we investigated the role of Rac in NK cell mediated anti-cryptococcal killing. We found thatCryptococcus neoformansindependently activates both Rac and SFK pathways in NK cells, and unlike in tumor killing,Cryptococcusinitiated a novel Rac → PI3K → Erk cytotoxicity cascade. Remarkably, Rac was not required for conjugate formation, despite its essential role in NK cytotoxicity againstC. neoformans Taken together, our data show that, unlike observations with tumor cells, NK cells use a novel Rac cytotoxicity pathway in conjunction with SFK, to killC. neoformans.

추출된 의학 개체 (NER)

유형영어 표현한국어 / 풀이UMLS CUI출처등장
시술 botulinum toxin 보툴리눔독소 주사 dict 1

MeSH Terms

Cell Line, Tumor; Class Ia Phosphatidylinositol 3-Kinase; Cryptococcus neoformans; Cytotoxicity, Immunologic; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Killer Cells, Natural; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Primary Cell Culture; Pyrones; Quinolines; RNA, Small Interfering; Signal Transduction; rac GTP-Binding Proteins; rac1 GTP-Binding Protein; src-Family Kinases; RAC2 GTP-Binding Protein

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