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PMID:19151721

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Citation

Cruz-Munoz, ME, Dong, Z, Shi, X, Zhang, S and Veillette, A (2009) Influence of CRACC, a SLAM family receptor coupled to the adaptor EAT-2, on natural killer cell function. Nat. Immunol. 10:297-305

Abstract

CRACC is a self-associating member of the signaling lymphocytic activation molecule family that is expressed on cells of the immune system, including natural killer cells and activated T cells. Here we examine the function and mechanism of action of CRACC using several complementary approaches, including the generation of a CRACC-deficient mouse. Our results demonstrate that CRACC positively regulated natural killer cell functions by a mechanism dependent on the adaptor EAT-2 but not the related adaptor SAP. However, in the absence of EAT-2, CRACC potently inhibited natural killer cell function. CRACC was also inhibitory in T cells, which are typically devoid of EAT-2. Thus, CRACC can exert activating or inhibitory influences on cells of the immune system depending on cellular context and the availability of effector proteins.

Links

PubMed Online version:10.1038/ni.1693

Keywords

Adaptor Proteins, Signal Transducing; Animals; Gene Expression Profiling; Killer Cells, Natural/immunology; Killer Cells, Natural/metabolism; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Receptors, Immunologic/immunology; Receptors, Immunologic/metabolism; T-Lymphocytes/immunology; T-Lymphocytes/metabolism; Transcription Factors/immunology; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SH21B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8BHK6

F

Seeded From UniProt

complete

MOUSE:SH21A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9QUM4

F

Seeded From UniProt

complete

HUMAN:FYN

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8BHK6

F

Seeded From UniProt

complete

MOUSE:SH21C

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8BHK6

F

Seeded From UniProt

complete

MOUSE:SH21C

acts_upstream_of_or_within

GO:0032814: regulation of natural killer cell activation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1922595

P

Seeded From UniProt

complete

MOUSE:SLAF7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q45HK4

F

Seeded From UniProt

complete

MOUSE:SLAF7

acts_upstream_of_or_within

GO:0032814: regulation of natural killer cell activation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:3622649

P

Seeded From UniProt

complete

MOUSE:SLAF7

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SLAF7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O35324

F

Seeded From UniProt

complete

MOUSE:SLAF7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P06241

F

Seeded From UniProt

complete

MOUSE:SLAF1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O88890

F

Seeded From UniProt

complete


See also

References

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