烟酸代谢
中文名称
通路描述
烟酸（烟酰胺）和烟酰胺腺嘌呤二核苷酸（NAD+）以及烟酰胺腺嘌呤二磷酸（NADP+）是许多氧化还原反应的必需辅因子。生成 NAD+ 的细胞质反应可分为三组（Cambronne & Krause 2020; Covarrubias et al. 2021; Magni et al. 2004）。第一组是在从头或色氨酸降解途径中，由色氨酸降解产生的 ACS 自发转化为 QUIN，随后依次转化为 NAMN、NAAD 和 NAD+，这些反应由 QPRT、NMNAT2 和 NADSYN1 催化。第二组是在 PreissâHandler 途径中，由 SLC22A13 或 SLC5A3 转运入细胞外烟酸（NCA）转化为烟酸 D-核糖核苷酸（NAMN），该物质可进入从头途径转化为 NAD+。其余大组反应调节烟酰胺（NAM）水平并再生 NAD+ 来自各种代谢中间体。在此过程中起关键作用的酶包括烟酰胺磷酸核糖转移酶（NAMPT）和烟酸磷酸核糖转移酶（NAPRT1）。尽管这些酶在烟酰胺利用中很重要，但在人类中它们尚未充分表征。NAM 水平还受烟酰胺 N-甲基转移酶（NNMT）调节，该酶可能是饮食诱导肥胖的潜在调节剂（Kraus et al. 2014）。包括位于细胞核、线粒体和过氧化物酶体中的部分过程的反应也包含在此通路中。
英文描述
Signaling by NTRK3 (TRKC) NTRK3 (TRKC) belongs to the family of neurotrophin receptor tyrosine kinases, which also includes NTRK1 (TRKA) and NTRK2 (TRKB). Neurotrophin-3 (NTF3, also known as NT-3) is the ligand for NTRK3. Similar to other NTRK receptors and receptor tyrosine kinases in general, ligand binding induces receptor dimerization followed by trans-autophosphorylation on conserved tyrosines in the intracellular (cytoplasmic) domain of the receptor (Lamballe et al. 1991, Philo et al. 1994, Tsoulfas et al. 1996, Yuen and Mobley 1999, Werner et al. 2014). These conserved tyrosines serve as docking sites for adaptor proteins that trigger downstream signaling cascades. Signaling through PLCG1 (Marsh and Palfrey 1996, Yuen and Mobley 1999, Huang and Reichardt 2001), PI3K (Yuen and Mobley 1999, Tognon et al. 2001, Huang and Reichardt 2001, Morrison et al. 2002, Lannon et al. 2004, Jin et al. 2008) and RAS (Marsh and Palfrey 1996, Gunn-Moore et al. 1997, Yuen and Mobley 1999, Gromnitza et al. 2018), downstream of activated NTRK3, regulates cell survival, proliferation and motility.In the absence of its ligand, NTRK3 functions as a dependence receptor and triggers BAX and CASP9-dependent cell death (Tauszig-Delamasure et al. 2007, Ichim et al. 2013).NTRK3 was reported to activate STAT3 through JAK2, but the exact mechanism has not been elucidated (Kim et al. 2016). NTRK3 was reported to interact with the adaptor protein SH2B2, but the biological role of this interaction has not been determined (Qian et al. 1998).Receptor protein tyrosine phosphatases PTPRO and PTPRS (PTPsigma) negatively regulate NTRK3 signaling by dephosphorylating NTRK3 (Beltran et al. 2003, Faux et al. 2007, Hower et al. 2009, Tchetchelnitski et al. 2014). In addition to dephosphorylation of NTRK3 in-cis, the extracellular domain of pre-synaptic PTPRS can bind in-trans to extracellular domain of post-synaptic NTRK3, contributing to synapse formation (Takahashi et al. 2011, Coles et al. 2014).
所含基因
4 个基因