2B4*

Protein 2B4*

Identifiers
HUGO:CD244

References
CASCADE:2B4
CASCADE:KIR2DL1
NATURAL_KILLER
PMID:16081768, PMID:15905190, PMID:15905190
2B4 works as activator in human model and as inhibitor of NK activity in mouse model.
NK cells costimulate each other through 2B4-CD48 interactions
The cytoplasmic domains of murine 2B4L and human 2B4 contain three
and four immunoreceptor tyrosine-based switch motifs (ITSM)
Upon engagement, the receptor
is recruited to lipid rafts at the target cell interface in an actin-dependent
manner, and tyrosine residues in the ITSM sequences are phosphorylated
. Phosphorylation of the ITSM sequences creates specific binding sites
for SAP (SH2D1A). SAP is an SH2 domain-containing adaptor that links 2B4 to the
Src family PTK Fyn.
PMID:17171759
The regulation of SAP has functional consequences for the stimulation of NK cell cytotoxicity by 2B4. In resting NK cells, 2B4 stimulation can only enhance NK cell lysis when co-triggered with other activating NK cell receptors. In IL-2-activated NK cells with high SAP expression the triggering of 2B4 alone is sufficient to induce NK cell cytotoxicity, demonstrating a correlation between the regulated SAP expression and the function of 2B4
PMID:20189481, PMID:22786724
2B4 signaling acts synergistically with NG2D and DNAM1 signalings in NK activation and tumor cells lysis.
It activates LCP2/VAV1/PCLG pathway.
PMID:15169881
2B4 signaling induces phosphorylation of SHIP1,VAV1,CBL.
This phosphorylation is dependent on SAP and FYN.
DNAM1 induces VAV1 pathway probably via LCP2 (SLP76).
It demonstrate synergy with 2B4 in activation of vav1 pathway.
PMID:12515815
Coengagement of inhibitory receptor KIR2DL1 blocked 2B4 phosphorylation and downstream signaling.
PMID:16339513
CLEC2D (LLT1) is a ligand for the inhibitory human KLRB1 (NKR-P1A) receptor.
LLT1 inhibits NK cytotoxicity induced by either the 2B4(CD48/CD244) pathway or the MICA/NKG2D pathway.

Modifications:
In compartment: INNATE_IMMUNE_CELL_Membrane

2B4*@INNATE_IMMUNE_CELL_Membrane
2B4*|pho@INNATE_IMMUNE_CELL_Membrane

Participates in complexes:
In compartment: INNATE_IMMUNE_CELL_Membrane

Participates in reactions:
As Reactant or Product:

As Catalyser: