Immunoreceptor tyrosine-based activation motif (ITAM)

The Immunoreceptor tyrosine-based activation motif (ITAM) is a sequence motif (consensus signature: YxxL/Ix_6–8_YxxL/I) repeated twice within the cytoplasmic domains of various immune receptors (e.g., CD3 chains of TCR, CD79 chains of BCR, Fc receptors, DAP12, FcRγ)[1][3][5]. Upon ligand engagement, ITAM tyrosines are phosphorylated by Src-family kinases. Phosphorylated ITAMs recruit SH2-domain proteins (notably Syk and ZAP-70 kinases), initiating intracellular signaling cascades resulting in immune cell activation, proliferation, and differentiation[1][3][5]. ITAMs are essential for adaptive immunity and are also involved in specialized functions such as osteoclast differentiation[4]. Aberrant ITAM signaling plays a role in autoimmune diseases, inflammation (e.g., rheumatoid arthritis), infection, and oncogenesis[4][6]. Therapeutic approaches typically target ITAM-associated receptors or signaling pathways, not the ITAM motif itself.

Other names

ITAMImmunoreceptor tyrosine activation motif