Mammalian tribbles homologs at the crossroads of endoplasmic reticulum stress and Mammalian target of rapamycin pathways.
Mammalian tribbles homologs at the crossroads of endoplasmic reticulum stress and Mammalian target of rapamycin pathways.
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作者：
Cunard R
2000年，研究人员发现了Tribbles，这是一种通过抑制有丝分裂来协调形态发生的果蝇蛋白。进一步的工作已经描绘了爪蟾（Xtrb2），线虫（Nipi-3）和果蝇tribbles的哺乳动物同源物，包括TRB1， TRB2和TRB3。tribbles同源物的序列是高度保守的，尽管它们具有蛋白激酶结构，但迄今为止尚未显示出具有激酶活性。TRB家族成员在巨噬细胞、淋巴细胞、肌肉细胞、脂肪细胞和成骨细胞的分化中发挥作用。TRB异构体还协调一些关键的细胞过程，包括糖和脂质代谢、炎症、细胞应激、生存、凋亡和肿瘤发生。TRB家族成员调节多种复杂信号网络，包括丝裂原激活的蛋白激酶级联、蛋白激酶B/AKT信号、哺乳动物雷帕霉素靶点和炎症途径。下面的综述将讨论果蝇的后生同源物，它们的结构、表达模式和功能。特别地，我们将关注TRB3在肾足细胞中的功能。本综述还将讨论tribbles蛋白相互作用的关键信号通路，并为开发利用这些相互作用的新疗法提供理论基础，为急性和慢性肾脏疾病提供更好的治疗选择。
In 2000, investigators discovered Tribbles, a Drosophila protein that coordinates morphogenesis by inhibiting mitosis. Further work has delineated Xenopus (Xtrb2), Nematode (Nipi-3), and mammalian homologs of Drosophila tribbles, which include TRB1, TRB2, and TRB3. The sequences of tribbles homologs are highly conserved, and despite their protein kinase structure, to date they have not been shown to have kinase activity. TRB family members play a role in the differentiation of macrophages, lymphocytes, muscle cells, adipocytes, and osteoblasts. TRB isoforms also coordinate a number of critical cellular processes including glucose and lipid metabolism, inflammation, cellular stress, survival, apoptosis, and tumorigenesis. TRB family members modulate multiple complex signaling networks including mitogen activated protein kinase cascades, protein kinase B/AKT signaling, mammalian target of rapamycin, and inflammatory pathways. The following review will discuss metazoan homologs of Drosophila tribbles, their structure, expression patterns, and functions. In particular, we will focus on TRB3 function in the kidney in podocytes. This review will also discuss the key signaling pathways with which tribbles proteins interact and provide a rationale for developing novel therapeutics that exploit these interactions to provide better treatment options for both acute and chronic kidney disease.