Identifiers
HUGO:SH2D1B
References
NATURAL_KILLER
CASCADE:2B4
PMID:25312647, PMID:19151721
SLAMF7 mediates activating or inhibitory effects in NK cells, depending on whether cells express (activating) or do not express (inhibiting) the adaptor SH2D1B (EAT-2).
SLAMF7 binds SH2D1B (EAT-2) via phosphorylated tyrosine 281 (Y281) in its cytoplasmic segment, thereby triggering activating signals.
PMID:16339536, PMID:24687958, PMID:PMID:19151721
SH2D1B (EAT-2) also associates with 2B4 predominantly in resting NK cells, whereas SAP preferentially binds 2B4 upon activation.
Tyrosine phosphorylation of cytoplasmic ITSMs of 2B4 augments their affinity for SAP, while reducing the affinity for EAT-2.
Ligation of CRACC induces the activation of PLC??1 and PLC??2 and PI3K signaling pathways
Ligation of CRACC induced modest tyrosine phosphorylation of the guanine nucleotide exchange factors Vav and the 5??? inositol phosphatase SHIP-1 and E3 ubiquitin ligase c-Cbl
probably via EAT2.Conserved C-terminal tyrosine (Y127) is critical for activating function of human EAT-2.
EAT-2 stimulates granule polarization by way of Y127 and Ca2+ fluxes.
→ 2B4*@INNATE_IMMUNE_CELL_Membrane + SH2D1B@INNATE_IMMUNE_CELL_Membrane
+ in_s1747 → SH2D1B|pho:SLAMF7|pho|hm2@INNATE_IMMUNE_CELL_Membrane
→ PI3KR(p85)*@INNATE_IMMUNE_CELL_Cytosol
→ VAV1|pho|active@INNATE_IMMUNE_CELL_Cytosol
→ PLCG2|pho@INNATE_IMMUNE_CELL_Cytosol
→ PLCG1|pho@INNATE_IMMUNE_CELL_Cytosol
→ CBL|pho|active@INNATE_IMMUNE_CELL_Cytosol