Table 1.

Critical signaling molecules that regulate the development, cytotoxicity, or cytokine production from NK cells.

Signaling protein	Function	Method	Development	Cytotoxicity	Inflammatory cytokines	Our publication
Lck	Membrane proximal kinase	siRNA/pharmacological inhibitor	Not applicable	Reduced	Reduced
Fyn	Membrane proximal kinase	Knockout	Unknown	Reduced	significantly increased	Rajasekaran et al. (47)
LAT	Scaffold protein	siRNA	Not applicable	Reduced	Reduced
PLC-γ1	Second messenger generation	Knockout and gene reconstituion	Partial defect in development	Not affected	Not affected	Regunathan et al. (49)
PLC-γ2	Second messenger generation	Knockout and gene preconstituion	Increased NK precursors, Impaired terminal maturation	Significantly impaired	Significantly impaired
PI3K-p85α	Regulatory subunit of PI3K	Knockout	Impaired terminal maturation, Decreased NK cells	Significantly impaired	Significantly impaired	Awasthi et al. (50)
PI3K-p110δ	Catalytic subunit of PI3K	Knockin	Impaired terminal maturation, decreased NK cells	Significantly impaired	Significantly impaired	Guo et al. (51)
Rap1a	Small GTPase	Knockout	Not affected	Not affected	Not affected	Awasthi et al. (50)
Rap1b	Small GTPase	Knockout	Not affected	Not affected	Significantly impaired
Carma1	CARD domain-containing scaffold	Knockout/CARD domain deletion	Not affected	Moderately impaired	Significantly impaired	Rajasekaran et al. (48, 52)
Bcl10	CARD domain-containing scaffold	Knockout	Not affected	Moderately impaired	Significantly impaired	Malarkannan et al. (53)
TAK1	MAPKKK	Conditional knockout	Not applicable	Moderately impaired	Significantly impaired	Rajasekaran et al. (48, 52)
ADAP	Scaffold protein	Knockout	Unknown	Not affected	Significantly impaired	Rajasekaran et al. (48)