Function of novel molecule Gasp exclusively expressed in the thymus

我们发现了一个新的基因Gasp（Themis），这是专门在胸腺中表达，并报告说，Themis是胸腺细胞的积极选择的关键。Themis是一种独特的分子，它是正向选择所绝对需要的，但不是负向选择和稳态扩张所必需的。Themis与Grb 2组成性相关，并且在TCR刺激后酪氨酸磷酸化，因此可能参与TCR依赖性信号转导。它还参与TCR依赖性IL-2的产生，然而，我们没有观察到任何调节信号强度的迹象。从Themis的结构域缺失分析，两个CABIT结构域，一个富含脯氨酸的序列（PRS）和一个核定位信号（NLS）都被证明是其功能所必需的。总的来说，Themis不仅仅是调节信号的强度，而且可能对维持胸腺中正选择所需的弱信号很重要。Themis的分子机制尚不清楚，但目前的研究揭示了其在IL-2产生中的重要性，以及两个CABIT结构域的差异功能。Themis可能不像其他信号转导子那样简单地调节信号强度，而是参与细胞内信号转导的时空调控。

We identified a novel gene Gasp (Themis), which is exclusively expressed in the thymus and reported that Themis is critical in positive selection of thymocytes. Themis is a unique molecule that is absolutely required for positive selection, but is not required for negative selection and homeostatic expansion. Themis constitutively associates with Grb2 and tyrosine phosphorylated upon TCR-stimulation, therefore likely to be involved in TCR-dependent signal transduction. It is also involved in TCR-dependent IL-2 production, however, we could not observe any sign of modulating signaling strength. From domains deletion analysis of Themis, two of CABIT domains, a proline rich sequence (PRS), and a nuclear localization signal (NLS) are all shown to be required for its function. Collectively, Themis is not simply modulating strength of signal, but may be important for sustaining weak signal required for positive selection in the thymus. Molecular mechanism of Themis is still not well known, however, the current study unveiled its importance for IL-2 production, and differential function of the two CABIT domains. Themis may not simply modulate signaling strength like other signal transducers, but it may involved in spatiotemporal regulation of intracellular signal transduction.