STAM,也称为STAM1或信号转导和激活分子1,是一种重要的细胞内衔接蛋白。STAM属于Hermes家族,与STAM2(也称为STAM2或Hrs)在结构上相似,但功能上有所不同。STAM在多种生物学过程中发挥重要作用,包括细胞信号传导、内吞作用、溶酶体形成和免疫反应。
STAM在细胞信号传导中发挥重要作用,尤其是与Toll样受体(TLR)信号通路相关。TLR是一类模式识别受体,能够识别病原体相关的分子模式(PAMPs),并激活免疫反应。STAM与TLR相关蛋白MyD88相互作用,参与TLR信号通路的激活和下游信号传导。STAM还与TRAF6相互作用,参与NF-κB信号通路的激活,从而调节免疫反应和炎症反应[1]。
STAM在内吞作用和溶酶体形成中也发挥重要作用。STAM与多种内吞相关蛋白相互作用,如AP-2和Eps15,参与内吞小泡的形成和转运。STAM还与溶酶体相关蛋白Lamp2相互作用,参与溶酶体的形成和功能调节[2]。
在免疫反应中,STAM也发挥重要作用。STAM与FcεRI相互作用,参与肥大细胞的活化。STAM还与FcγRIIb相互作用,参与B细胞的免疫调节。此外,STAM还与FcRn相互作用,参与IgG的转运和稳定性调节[3]。
STAM在多种疾病中发挥重要作用,包括肿瘤、炎症和代谢性疾病。在肿瘤中,STAM的异常表达与肿瘤的发生和发展相关。例如,STAM的表达在结直肠癌和胃癌中升高,并且与不良预后相关[4,5]。在炎症中,STAM的异常表达与炎症性疾病的发生和发展相关。例如,STAM的表达在类风湿性关节炎和系统性红斑狼疮中升高,并且与疾病的活动性相关[6,7]。在代谢性疾病中,STAM的异常表达与非酒精性脂肪性肝病(NAFLD)和非酒精性脂肪性肝炎(NASH)的发生和发展相关。例如,STAM的表达在NASH小鼠模型中升高,并且与脂肪肝的形成和肝细胞癌的发生相关[8]。
综上所述,STAM是一种重要的细胞内衔接蛋白,在细胞信号传导、内吞作用、溶酶体形成和免疫反应中发挥重要作用。STAM在多种疾病中发挥重要作用,包括肿瘤、炎症和代谢性疾病。STAM的研究有助于深入理解细胞内信号传导和免疫调节的机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Welsh, Joshua A, Goberdhan, Deborah C I, O'Driscoll, Lorraine, Théry, Clotilde, Witwer, Kenneth W. . Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. In Journal of extracellular vesicles, 13, e12404. doi:10.1002/jev2.12404. https://pubmed.ncbi.nlm.nih.gov/38326288/
2. Li, Zhenyang, Zhou, Ye, Jia, Kaiwei, Cao, Xuetao, Hou, Jin. 2022. JMJD4-demethylated RIG-I prevents hepatic steatosis and carcinogenesis. In Journal of hematology & oncology, 15, 161. doi:10.1186/s13045-022-01381-6. https://pubmed.ncbi.nlm.nih.gov/36333807/
3. Märkle, Hanna, Saur, Isabel M L, Stam, Remco. . Evolution of resistance (R) gene specificity. In Essays in biochemistry, 66, 551-560. doi:10.1042/EBC20210077. https://pubmed.ncbi.nlm.nih.gov/35612398/
4. Weiß, Claudia, Ziegler, Andreas, Becker, Lena-Luise, von der Hagen, Maja, Kaindl, Angela M. 2021. Gene replacement therapy with onasemnogene abeparvovec in children with spinal muscular atrophy aged 24 months or younger and bodyweight up to 15 kg: an observational cohort study. In The Lancet. Child & adolescent health, 6, 17-27. doi:10.1016/S2352-4642(21)00287-X. https://pubmed.ncbi.nlm.nih.gov/34756190/
5. Yang, Haoran, Deng, Qingmei, Ni, Tun, Wang, Hongzhi, Yang, Wulin. 2021. Targeted Inhibition of LPL/FABP4/CPT1 fatty acid metabolic axis can effectively prevent the progression of nonalcoholic steatohepatitis to liver cancer. In International journal of biological sciences, 17, 4207-4222. doi:10.7150/ijbs.64714. https://pubmed.ncbi.nlm.nih.gov/34803493/
6. Weiß, Claudia, Becker, Lena-Luise, Friese, Johannes, Johannsen, Jessika, Ziegler, Andreas. 2024. Efficacy and safety of gene therapy with onasemnogene abeparvovec in children with spinal muscular atrophy in the D-A-CH-region: a population-based observational study. In The Lancet regional health. Europe, 47, 101092. doi:10.1016/j.lanepe.2024.101092. https://pubmed.ncbi.nlm.nih.gov/39434961/
7. Xie, Ying, Huang, Yu, Li, Zhi-Yong, Yin, Zhinan, Lin, Xue-Jia. 2024. Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells. In Molecular cancer, 23, 95. doi:10.1186/s12943-024-02001-2. https://pubmed.ncbi.nlm.nih.gov/38720319/
8. de Groot, Pieter, Nikolic, Tanja, Pellegrini, Silvia, Roep, Bart, Nieuwdorp, Max. 2020. Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial. In Gut, 70, 92-105. doi:10.1136/gutjnl-2020-322630. https://pubmed.ncbi.nlm.nih.gov/33106354/