角质硫酸降解
中文名称
通路描述
角质硫酸蛋白聚糖（KSPGs）在溶酶体中降解，作为糖蛋白正常稳态的一部分。糖蛋白必须完全降解以避免未消化的片段积累并引发多种溶酶贮积病。KSPGs 是 N-连接的糖蛋白，由外糖苷酶作用释放糖单糖。降解的主要步骤展示了发生裂解反应的类型，以表示完整的 KS 降解，此处未显示糖蛋白核心蛋白的蛋白酶解（Winchester 2005, Aronson & Kuranda 1989）。
英文描述
Signaling by FLT3 ITD and TKD mutants FLT3 is subject to internal tandem duplications (ITDs) of lengths varying from 3 to 1236 base pairs (Nakao et al, 1996; Kiyoi et al 1997, Meshinchi et al, 2008; reviewed in Kazi and Roonstrand, 2019). These ITDs are generally found in the juxtamembrane domain, or more rarely, the first tyrosine kinase domain (TKD) and disrupt the autoinhibitory loop of the receptor, constitutively activating it (Kiyoi et al, 2002; Griffith et al, 2004; reviewed in Lagunas-Rangel and Chavez-Valencia, 2017; Kazi and Roonstrand, 2019). FLT3 ITDs are found in ~25% of acute myeloid leukemias (AMLs) and represent the most frequent mutation of this cancer (reviewed in Kazi and Roonstrand, 2019, Klug et al, 2018)
At lower frequency, FLT3 is subject to activating point mutations (~7% of AML cases). These mutations tend to cluster in the TKD, with mutation of the activation loop residue D835 and the gatekeeper F691 residue the most common sites (Griffin et al, 2001; Jiang et al, 2004; reviewed in Kazi and Roonstrand, 2019).
FLT3 ITD and TKD mutants support cellular transformation through activation of downstream signaling pathways such as the MAP kinase, PI3K/AKT and STAT5 cascades. There is some debate about the extent to which the pathways activated by the ITD and TKD mutants are distinct, with some evidence that STAT5 signaling, in particular, is more characteristic of FLT3 ITD activation (Hayakawa et al, 2000; Choudhary et al, 2005; Grundler et al, 2005; Choudhary et al, 2007; Yoshimoto et al, 2009; Leischner et al, 2012; Janke et al, 2014; Marhall et al, 2018; reviewed in Chan, 2011; Kazi and Roonstrand, 2019).
At lower frequency, FLT3 is subject to activating point mutations (~7% of AML cases). These mutations tend to cluster in the TKD, with mutation of the activation loop residue D835 and the gatekeeper F691 residue the most common sites (Griffin et al, 2001; Jiang et al, 2004; reviewed in Kazi and Roonstrand, 2019).
FLT3 ITD and TKD mutants support cellular transformation through activation of downstream signaling pathways such as the MAP kinase, PI3K/AKT and STAT5 cascades. There is some debate about the extent to which the pathways activated by the ITD and TKD mutants are distinct, with some evidence that STAT5 signaling, in particular, is more characteristic of FLT3 ITD activation (Hayakawa et al, 2000; Choudhary et al, 2005; Grundler et al, 2005; Choudhary et al, 2007; Yoshimoto et al, 2009; Leischner et al, 2012; Janke et al, 2014; Marhall et al, 2018; reviewed in Chan, 2011; Kazi and Roonstrand, 2019).
所含基因
6 个基因