Cutting edge: human 2B4, an activating NK cell receptor, recruits the protein tyrosine phosphatase SHP-2 and the adaptor signaling protein SAP.

Signaling Protein SAP Phosphatase SHP-2 and the Adaptor Cell Receptor, Recruits the Protein Tyrosine Cutting Edge: Human 2B4, an Activating NK

The cytotoxicity receptor CRACC (CS-1) recruits EAT-2 and activates the PI3K and phospholipase Cgamma signaling pathways in human NK cells.

The CD2-like receptor-activating cytotoxic cell (CRACC) is a cell surface receptor of the CD2 family that triggers NK cell-mediated cytotoxicity through an undefined signaling pathway. CRACC contains cytoplasmic tyrosine-based motifs, immunoreceptor tyrosine-based switch motifs, which resemble those found in the NK cell receptor 2B4. In 2B4, these motifs recruit the adaptor signaling lymphocyti...

Molecular basis for positive and negative signaling by the natural killer cell receptor 2B4 (CD244).

Triggering of 2B4 (CD244) can induce natural killer (NK)-cell activation, costimulation, or even inhibition of NK-cell activity. Here, we investigate the molecular basis for the different signals generated by 2B4. We show that the first immunoreceptor tyrosine-based switch motif (ITSM) within the cytoplasmic tail of 2B4 is sufficient for 2B4-mediated NK-cell activation, whereas the third ITSM c...

Regulation of natural cytotoxicity by the adaptor SAP and the Src-related kinase Fyn

SAP is an adaptor protein that is expressed in NK and T cells. It is mutated in humans who have X-linked lymphoproliferative (XLP) disease. By interacting with SLAM family receptors, SAP enables tyrosine phosphorylation signaling of these receptors by its ability to recruit the Src-related kinase, Fyn. Here, we analyzed the role of SAP in NK cell functions using the SAP-deficient mouse model. O...

SHP-1- and phosphotyrosine-independent inhibitory signaling by a killer cell Ig-like receptor cytoplasmic domain in human NK cells.

Killer cell Ig-like receptors (KIR) are MHC class I-binding immunoreceptors that can suppress activation of human NK cells through recruitment of the Src homology 2-containing protein tyrosine phosphatase-1 (SHP-1) to two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic domains. KIR2DL4 (2DL4; CD158d) is a structurally distinct member of the KIR family, which is expr...