In this Perspective, we review the molecular interactions of ITAM- and ITIM-bearing proteins and consider their importance in regulating the outcome of immune cell stimulation by antigens.

ITIMs (immunoreceptor tyrosine-based inhibition motif; S/I/V/LxYxxI/V/L) and ITAMs (immunoreceptor tyrosine-based activation motif; consensus sequence YxxI/Lx 6-12 YxxI/L) are phosphorylation motifs found in a large number of receptors or adaptor proteins.

ITIM-containing receptors often serve to target immunoreceptor tyrosine-based activation motif (ITAM)-containing receptors, resulting in an innate inhibition mechanism within cells. [3] ITIM bearing receptors have important role in regulation of immune system allowing negative regulation at different levels of the immune response .

顾名思义，ITAM的存在可以激活免疫细胞，ITIM则抑制免疫细胞（虽然某些特殊情况ITAM起抑制作用）。 从分子机制上看，ITAM上的酪氨酸磷酸化后主要招募含有SH2的酪氨酸激酶蛋白（如 Syk， ZAP-70），而ITIM被磷酸化后招募SHP-1/2等磷酸水解酶，起到抑制激酶活性的作用。 另一类不受酪氨酸磷酸化调控的常见跨膜信号转导受体叫做 G蛋白偶联受体 (G protein coupled receptor，GPCR)，这类受体的共同结构特点是有7个跨膜α螺旋结构域，且C端和5-6号α螺旋 …

Immunoreceptor tyrosine-based activation motif (ITAM), (in the antagonistic case ITIM, I refers inhibition) is found in the tails of important cell signaling molecules involved in cell signaling transduction especially in immune system, including the T cell receptor complex (CD3 and ζ-chains), the B cell receptor complex (CD79-alpha and -beta ch...

2011年4月19日 · Immunoreceptor tyrosine-based activation motifs (ITAMs) are used by multiple receptors to activate immune cells. However, ITAM-associated receptors can have paradoxically inhibitory effects, which have been implicated in regulation of inflammatory responses, but mechanisms of inhibitory signaling are poorly understood.

Using platelet endothelial cell adhesion molecule 1 (PECAM-1) as a prototypical ITIM-bearing receptor, we demonstrate that initiation of inhibitory signaling occurs via a novel, sequential process in which Src family kinases phosphorylate the C-terminal ITIM, thereby enabling phosphorylation of the N-terminal ITIM of PECAM-1 by other Src homolog...

（1）itim是免疫受体酪氨酸抑制基序的英文缩写,基本组成是:i(异亮)/v(缬)xy(酪)xxl(亮),其酪氨酸被磷酸化后,可招募蛋白酪氨酸磷酸酶(ptp),并使之活化,ptk参与的激活信号转导通路即被截断.活化t细胞表达的ctla-4,胞浆中有itim,当b7与ctla-4结合时给予已活化t细胞抑制信号.

这些基序被称为“ itam”和“ itim”，用于基于免疫受体酪氨酸的激活（或抑制）基序，为两个相对的信号模块提供了基础，这些模块在控制免疫系统中的细胞活化方面进行了对决。

In this review, we summarize the diverse functions employed by microglia in response to Aβ plaques and also discuss the innate immune receptors and intracellular signaling players that guide these functions. Specifically, we focus on the role of ITAM and ITIM signaling cascades in regulating microglia innate immune responses.