This list is reportedly expanded by studying rare human SNPs that create the consensus signature S/I/V/LxYxxI/V/L motif.
This may be achieved by co-crosslinking with an ITAM motif of activating receptor that recruits a Src family kinase.
The dephosphorylation of cell activation critical substrates results due to phosphorylated ITIM's serving as recruitment sites for SHP-1 and SHP-2.
Subsequently, phospholipase Cy and phosphatidylinositol 3-kinase (PLCy and PI3-K) are activated, together leading to the production of phosphoinositol messengers and increase in cytoplasmic Ca2+.
Many ITIM-bearing receptors recruit SHP-1 and/or SHP-2 including KIRs, ILT, Ly49, LAIR-1, CD22, CD72 and Signal Regulatory Protein SIRPα.
SHP-1 and SHP-2 are structurally related protein tyrosine phosphatases but have different expression patterns and biological functions.
SHP-2 is ubiquitously expressed and is considered a positive regulator of cytokine and growth factor receptor signaling.
[14] ITIMs can also work in conjunction with immunoreceptor tyrosine-based switch motifs (ITSM) in order to activate ITIM-bearing receptors such as SHP-2.
(Modified according to[19]) On the basis of the inhibitory effects of FcγRIIB, a lot of prototypic molecules was constructed and used for developing new therapeutic approaches of allergies.
[19] In selected human malignancies such as acute myeloid leukemia, allogeneic hematopoietic cell transplantations have shown that the development of donor NK cells in recipient patients lacking donor KIR ligands can lead to improved engraftment and post-transplant survival by boosting graft-versus-leukemia effect in the absence of graft-versus-host disease.