Immunoreceptor tyrosine-based activation motif-bearing receptor (ITAM-bearing receptor)

Immunoreceptor tyrosine-based activation motif (ITAM)-bearing receptors are a diverse group of cell-surface proteins characterized by the presence of one or more ITAMs (sequence YxxL/I-x(6-12)-YxxL/I) in their cytoplasmic domains or associated signaling subunits, such as CD3ζ, CD79α/β, or DAP12 [PMID: 10700155]. These receptors are fundamental to the activation of T cells, B cells, natural killer (NK) cells, and myeloid cells, serving as the primary triggers for the adaptive and innate immune responses [PMID: 26011243]. Upon ligand binding, Src-family kinases phosphorylate the ITAM tyrosines, creating docking sites for tandem SH2-domain-containing kinases like Syk or ZAP-70, which then propagate signals leading to calcium mobilization, cytokine production, and cellular proliferation [PMID: 19144317, PMID: 21245915]. Dysregulation of ITAM signaling is a hallmark of various pathologies, including chronic inflammatory diseases, hematologic malignancies, and neurodegenerative conditions such as Alzheimer's disease, where the ITAM-bearing receptor TREM2 plays a critical role in microglial function [PMID: 30531978]. Therapeutic strategies targeting these receptors include monoclonal antibodies that deplete specific immune populations (e.g., anti-CD3 or anti-CD20) and small-molecule inhibitors that block downstream kinases like Syk to treat autoimmune disorders [PMID: 29346330].

Other names

ITAM-containing receptorITAM-coupled receptorActivating immunoreceptorITAM-signaling receptor

Modulation of immune cell activation through the phosphorylation of conserved tyrosine residues within the ITAM motif, which facilitates the recruitment and activation of SH2-domain-containing kinases such as Syk or ZAP-70 to initiate downstream signaling pathways [PMID: 19144317, PMID: 26011243].