The expanding role for ITAM-based signaling pathways in immune cells.
The expanding role for ITAM-based signaling pathways in immune cells.
复制标题
DOI：
10.1126/stke.3772007re2
复制
发表时间：
2007-03-13
期刊：
影响因子：
--
通讯作者：
Lowell, Clifford A
中科院分区：
文献类型：
--
作者：
Abram, Clare L;Lowell, Clifford A
基于免疫受体酪氨酸的激活基序（ITAM）是经典免疫受体（例如B和T淋巴细胞上的抗原受体和髓样细胞上的Fc受体（FcR））使用的主要信号传导结构域。ITAM包含在与这些受体相关的亚基的细胞内区域中，通常成对，或者是受体本身的胞质结构域的一部分。许多研究人员的数据表明，ITAM对于启动所有免疫受体下游的信号传导来说是必要且足够的。最近的报道表明，ITAM信号传导被经典免疫受体以外的其他受体使用：细胞粘附分子（整合素和PSGL-1），趋化因子受体（CXCR 4），丛蛋白和凝集素受体都通过ITAM样信号传导途径介导免疫细胞功能。白细胞中细胞内信号传导途径的这种会聚阐明了基于酪氨酸的激活基序在免疫系统中的重要性，并表明ITAM信号传导的抑制剂可能具有比最初设想的更广泛的作用。
The immunoreceptor tyrosine-based activation motif (ITAM) is the primary signaling domain used by classical immunoreceptors, such as the antigen receptors on B and T lymphocytes and the Fc receptors (FcRs) on myeloid cells. The ITAM is contained in the intracellular region of subunits associated with these receptors, often in pairs, or is part of the cytoplasmic domain of the receptors themselves. Data from many investigators have demonstrated that ITAMs are both necessary and sufficient for initiation of signaling downstream of all immunoreceptors. More recent reports indicate that ITAM signaling is used by additional receptors beyond the classical immunoreceptors: Cell adhesion molecules (integrins and PSGL-1), chemokine receptors (CXCR4), plexins, and lectin receptors all mediate immune cell function through ITAM-like signaling pathways. This convergence of intracellular signaling pathways in leukocytes illuminates the importance of tyrosine-based activation motifs in the immune system and suggests that inhibitors of ITAM signaling may have broader effects than originally envisioned.