In activated mouse natural killer (NK) cells, the NKG2D receptor associates with two intracellular adaptors, DAP10 and DAP12, which trigger phosphatidyl inositol 3 kinase (PI3K) and Syk family protein tyrosine kinases, respectively. Here we show that cytotoxicity, but not cytokine production, is triggered by NKG2D in activated NK cells lacking either DAP12 or the Syk family members Syk and ZAP70. Inhibition of PI3K blocks this cytotoxicity, suggesting that the DAP10-PI3K pathway is sufficient to initiate NKG2D-mediated killing of target cells. Our results highlight signaling divergence in the effector functions of NKG2D and indicate that alternative associations between a receptor and its adaptors may provide a single receptor with a dual 'on-switch', giving mouse NK cells more choices through which to trigger cytotoxicity.
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Arase, H
;
Mocarski, ES
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Mocarski, ES
;
Campbell, AE
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Campbell, AE
;
Hill, AB
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Hill, AB
;
Lanier, LL
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Bakker, ABH
;
Hoek, RM
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Hoek, RM
;
Cerwenka, A
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Cerwenka, A
;
Blom, B
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Blom, B
;
Lucian, L
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Lucian, L
;
McNeil, T
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
McNeil, T
;
Murray, R
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Murray, R
;
Phillips, JH
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Phillips, JH
;
Sedgwick, JD
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Sedgwick, JD
;
Lanier, LL
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Tech Univ Munich, Inst Microbiol, Trogerstr 32, D-81675 Munich, GermanyFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Bauer, Stefan
;
Groh, Veronika
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Groh, Veronika
;
Wu, Jun
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Wu, Jun
;
Steinle, Alexander
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Steinle, Alexander
;
Phillips, Joseph H.
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Phillips, Joseph H.
;
Lanier, Lewis L.
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Lanier, Lewis L.
;
Spies, Thomas
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
机构:
Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USABrown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA
Biron, CA
;
Nguyen, KB
论文数: 0引用数: 0
h-index: 0
机构:
Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USABrown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA
Nguyen, KB
;
Pien, GC
论文数: 0引用数: 0
h-index: 0
机构:
Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USABrown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA
Pien, GC
;
Cousens, LP
论文数: 0引用数: 0
h-index: 0
机构:
Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USABrown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA
Cousens, LP
;
Salazar-Mather, TP
论文数: 0引用数: 0
h-index: 0
机构:
Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USABrown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Arase, H
;
Mocarski, ES
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Mocarski, ES
;
Campbell, AE
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Campbell, AE
;
Hill, AB
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Hill, AB
;
Lanier, LL
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Bakker, ABH
;
Hoek, RM
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Hoek, RM
;
Cerwenka, A
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Cerwenka, A
;
Blom, B
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Blom, B
;
Lucian, L
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Lucian, L
;
McNeil, T
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
McNeil, T
;
Murray, R
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Murray, R
;
Phillips, JH
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Phillips, JH
;
Sedgwick, JD
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
Sedgwick, JD
;
Lanier, LL
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Tech Univ Munich, Inst Microbiol, Trogerstr 32, D-81675 Munich, GermanyFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Bauer, Stefan
;
Groh, Veronika
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Groh, Veronika
;
Wu, Jun
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Wu, Jun
;
Steinle, Alexander
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Steinle, Alexander
;
Phillips, Joseph H.
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Phillips, Joseph H.
;
Lanier, Lewis L.
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Lanier, Lewis L.
;
Spies, Thomas
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
机构:
Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USABrown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA
Biron, CA
;
Nguyen, KB
论文数: 0引用数: 0
h-index: 0
机构:
Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USABrown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA
Nguyen, KB
;
Pien, GC
论文数: 0引用数: 0
h-index: 0
机构:
Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USABrown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA
Pien, GC
;
Cousens, LP
论文数: 0引用数: 0
h-index: 0
机构:
Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USABrown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA
Cousens, LP
;
Salazar-Mather, TP
论文数: 0引用数: 0
h-index: 0
机构:
Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USABrown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA