Sol Sherry Thrombosis Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Int J Mol Sci. 2023 May 23;24(11):9126. doi: 10.3390/ijms24119126.
The two members of the UBASH3/STS/TULA protein family have been shown to critically regulate key biological functions, including immunity and hemostasis, in mammalian biological systems. Negative regulation of signaling through immune receptor tyrosine-based activation motif (ITAM)- and hemITAM-bearing receptors mediated by Syk-family protein tyrosine kinases appears to be a major molecular mechanism of the down-regulatory effect of TULA-family proteins, which possess protein tyrosine phosphatase (PTP) activity. However, these proteins are likely to carry out some PTP-independent functions as well. Whereas the effects of TULA-family proteins overlap, their characteristics and their individual contributions to cellular regulation also demonstrate clearly distinct features. Protein structure, enzymatic activity, molecular mechanisms of regulation, and biological functions of TULA-family proteins are discussed in this review. In particular, the usefulness of the comparative analysis of TULA proteins in various metazoan taxa, for identifying potential roles of TULA-family proteins outside of their functions already established in mammalian systems, is examined.
UBASH3/STS/TULA 蛋白家族的两个成员已被证明在哺乳动物生物系统中对关键的生物学功能，包括免疫和止血，具有关键的调控作用。Syk 家族蛋白酪氨酸激酶介导的免疫受体酪氨酸基激活基序（ITAM）和 hemITAM 结合受体的信号负调控似乎是 TULA 家族蛋白下调作用的主要分子机制，这些蛋白具有蛋白酪氨酸磷酸酶（PTP）活性。然而，这些蛋白也可能具有一些非 PTP 依赖性的功能。尽管 TULA 家族蛋白的作用存在重叠，但它们的特征及其对细胞调控的个体贡献也表现出明显的不同特征。本文讨论了 TULA 家族蛋白的蛋白结构、酶活性、调控的分子机制和生物学功能。特别是，本文还检查了在各种后生动物类群中比较分析 TULA 蛋白的有用性，以鉴定 TULA 家族蛋白在已经确定的其在哺乳动物系统中的功能之外的潜在作用。
