JAK/STAT信号通路及其对昆虫免疫的调控
收稿日期: 2022-12-06
修回日期: 2023-01-10
网络出版日期: 2023-02-15
基金资助
国家自然科学基金项目(32072417)
JAK/STAT signaling pathway and its regulation on insect immunity
Received date: 2022-12-06
Revised date: 2023-01-10
Online published: 2023-02-15
Supported by
the National Natural Science Foundation of China(32072417)
JAK/STAT信号通路参与细胞的生长、分化、凋亡和免疫调节等重要的生物学过程，是细胞因子介导的最重要的信号转导途径之一。在昆虫中，JAK/STAT是一条相对保守的信号途径，与Toll途径和Imd途径共同作为主要免疫途径以抵御病原物入侵，在昆虫免疫、激素调控和其他生理调节过程中发挥着十分重要的作用。本文介绍了细胞因子受体超家族、JAKs家族、STATs家族和JAK/STAT信号通路及其负反馈调节的作用机制，分析了寄生物、病毒和真菌感染昆虫时，JAK/STAT信号通路的重要功能及最新研究进展，并提出了JAK/STAT信号通路研究中尚待解决的问题，以期为该领域后续深入研究提供方向和参考。
韦湘怡, 胡冬春, 高祖鹏, 冯从经 . JAK/STAT信号通路及其对昆虫免疫的调控[J]. 遗传, 2023 , 45(3) : 229 -236 . DOI: 10.16288/j.yczz.22-402
JAK/STAT signaling pathway is involved in important biological processes, such as cell growth, differentiation, apoptosis and immune regulation, and is one of the most important signal transduction pathways mediated by cytokines. JAK/STAT is a relatively conserved signaling pathway in insects, which is the main immune pathway together with Toll signaling pathway and Imd signaling pathway to resist the invasion of pathogens. It plays a vital role in insect immunity, hormone regulation and other physiological regulation processes. In this review, we summarize the cytokine receptor superfamily, JAKs family, STATs family, JAK/STAT signaling pathway and its mechanism of negative feedback regulation. We analyze the important functions and the latest research progress of JAK/STAT signaling pathway in insect infected by parasites, viruses and fungi. Finally, we propose the remaining problems in the study of JAK/STAT signaling pathway, so as to provide direction and reference for further research in this field.
Key words： JAK/STAT; insect immunity; signal transduction; negative regulations; cytokine
| [1] | Morris R, Kershaw NJ, Babon JJ. The molecular details of cytokine signaling via the JAK/STAT pathway. Protein Sci, 2018, 27(12): 1984-2009. |
| [2] | Dodington DW, Desai HR, Woo M. JAK/STAT-emerging players in metabolism. Trends Endocrinol Metab, 2018, 29(1): 55-65. |
| [3] | Barillas-Mury C, Han YS, Seeley D, Kafatos FC. Anopheles gambiae Ag-STAT, a new insect member of the STAT family, is activated in response to bacterial infection. EMBO J, 1999, 18(4): 959-967. |
| [4] | Lemaitre B, Hoffmann J. The host defense of Drosophila melanogaster. Annu Rev Immunol, 2007, 25: 697-743. |
| [5] | Hubbard SR. Mechanistic insights into regulation of JAK2 tyrosine kinase. Front Endocrinol (Lausanne), 2018, 8: 361. |
| [6] | Bousoik E, Montazeri AH. "Do We Know Jack" about JAK? A closer look at JAK/STAT signaling pathway. Front Oncol, 2018, 8: 287. |
| [7] | Glassman CR, Tsutsumi N, Saxton RA, Lupardus PJ, Jude KM, Garcia KC. Structure of a janus kinase cytokine receptor complex reveals the basis for dimeric activation. Science, 2022, 376(6589): 163-169. |
| [8] | Ferrao R, Wallweber HJA, Ho H, Tam C, Franke Y, Quinn J, Lupardus PJ.The structural basis for class II cytokine receptor recognition by JAK1. Structure, 2016, 24(6): 897-905. |
| [9] | Lupardus PJ, Skiniotis G, Rice AJ, Thomas C, Fischer S, Walz T, Garcia KC. Structural snapshots of full-length JAK1, a transmembrane gp130/IL-6/IL-6Rα cytokine receptor complex, and the receptor-JAK1 holocomplex. Structure, 2011, 19(1): 45-55. |
| [10] | Atanasova M, Whitty A. Understanding cytokine and growth factor receptor activation mechanisms. Crit Rev Biochem Mol Biol, 2012, 47(6): 502-530. |
| [11] | O'shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity, 2012, 36(4): 542-550. |
| [12] | Cai B, Cai JP, Luo YL, Chen C, Zhang S. The specific roles of JAK/STAT signaling pathway in sepsis. Inflammation, 2015, 38(4): 1599-1608. |
| [13] | Lafave LM, Levine RL. JAK2 the future: therapeutic strategies for JAK-dependent malignancies. Trends Pharmacol Sci, 2012, 33(11): 574-582. |
| [14] | O'Shea JJ, Pesu M, Borie DC, Changelian PS. A new modality for immunosuppression: targeting the JAK/STAT pathway. Nat Rev Drug Discov, 2004, 3(7): 555-564. |
| [15] | Trivedi S, Starz GM. Drosophila JAK/STAT signaling: regulation and relevance in human cancer and metastasis. Int J Mol Sci, 2018, 19(12) |
| [16] | Shen P, Wang YZ, Jia XX, Xu PF, Qin L, Feng X, Li ZY, Qiu ZX. Dual-target Janus kinase (JAK) inhibitors: comprehensive review on the JAK-based strategies for treating solid or hematological malignancies and immune- related diseases. Eur J Med Chem, 2022, 239: 114551. |
| [17] | Benucci M, Damiani A, Infantino M, Manfredi M, Lari B, Grossi V, Gobbi FL, Sarzi-Puttini P. Cardiovascular safety, cancer and Jak-inhibitors: differences to be highlighted. Pharmacol Res, 2022, 183: 106359. |
| [18] | Wilmes S, Hafer M, Vuorio J, Tucker JA, Winkelmann H, L?chte S, Stanly TA, Pulgar Prieto KD, Poojari C, Sharma V, Richter CP, Kurre R, Hubbard SR, Garcia KC, Moraga I, Vattulainen I, Hitchcock IS, Piehler J. Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations. Science, 2020, 367(6478): 643-652. |
| [19] | Babon JJ, Lucet IS, Murphy JM, Nicola NA, Varghese LN. The molecular regulation of janus kinase (JAK) activation. Biochem J, 2014, 462(1): 1-13. |
| [20] | Chen Q, Lv JJ, Yang WW, Xu BP, Wang Z, Yu ZH, Wu JW, Yang Y, Han YH. Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis. Theranostics, 2019, 9(22): 6424-6442. |
| [21] | Schindler C, Levy DE, Decker T. JAK-STAT signaling: from interferons to cytokines. J Biol Chem, 2007, 282(28): 20059-20063. |
| [22] | Rah B, Rather RA, Bhat GR, Baba AB, Mushtaq I, Farooq M, Yousuf T, Dar SB, Parveen S, Hassan R, Mohammad F, Qassim I, Bhat A, Ali S, Zargar MH, Afroze D. JAK/STAT signaling: molecular targets, therapeutic opportunities, and limitations of targeted inhibitions in solid malignancies. Front Pharmacol, 2022, 13:821344. |
| [23] | Darnell Jr JE, Kerr IM, Stark GR. JAK-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science, 1994, 264(5164): 1415-1421. |
| [24] | Sanpaolo ER, Rotondo C, Cici D, Corrado A, Cantatore FP. JAK/STAT pathway and molecular mechanism in bone remodeling. Mol Biol Rep, 2020, 47(11): 9087-9096. |
| [25] | Hou YY, Wang K, Wan WJ, Cheng Y, Pu X, Ye XF. Resveratrol provides neuroprotection by regulating the JAK2/STAT3/PI3K/AKT/mTOR pathway after stroke in rats. Genes Dis, 2018, 5(3): 245-255. |
| [26] | Johnson DE, O'keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol, 2018, 15(4): 234-248. |
| [27] | Yoshimura A, Nishinakamura H, Matsumura Y, Hanada T. Negative regulation of cytokine signaling and immune responses by SOCS proteins. Arthritis Res Ther, 2005, 7(3): 100-110. |
| [28] | Liau NPD, Laktyushin A, Lucet IS, Murphy JM, Yao SG, Whitlock E, Callaghan K, Nicola NA, Kershaw NJ, Babon JJ.The molecular basis of JAK/STAT inhibition by SOCS1. Nat Commun, 2018, 9(1): 1558. |
| [29] | Kausar S, Gul I, Liu RC, Ke XX, Dong Z, Abbas MN, Cui HJ. Antheraea pernyi suppressor of cytokine signaling 2 negatively modulates the JAK/STAT pathway to attenuate microbial infection. Int J Mol Sci, 2022, 23(18): 10389. |
| [30] | Bang IS. JAK/STAT signaling in insect innate immunity. Entomol Res, 2019, 49(8): 339-353. |
| [31] | Niu GJ, Xu JD, Yuan WJ, Sun JJ, Yang MC, He ZH, Zhao XF, Wang JX. Protein inhibitor of activated STAT (PIAS) negatively regulates the JAK/STAT pathway by inhibiting STAT phosphorylation and translocation. Front Immunol, 2018, 9: 2392. |
| [32] | Strand MR. The insect cellular immune response. Insect Sci, 2008, 15(1): 1-14. |
| [33] | Yang L, Wan B, Wang BB, Liu MM, Fang Q, Song QS, Ye GY. The pupal ectoparasitoid pachycrepoideus vindemmiae regulates cellular and humoral immunity of host Drosophila melanogaster. Front Physiol, 2019, 10:1282. |
| [34] | Honti V, Csordás G, Kurucz é, Márkus R, Andó I. The cell-mediated immunity of Drosophila melanogaster: hemocyte lineages, immune compartments, microanatomy and regulation. Dev Comp Immunol, 2014, 42(1): 47-56. |
| [35] | Yang H, Kronhamn J, Ekstr?m JO, Korkut GG, Hultmark D. JAK/STAT signaling in Drosophila muscles controls the cellular immune response against parasitoid infection. EMBO Rep, 2015, 16(12): 1664-1672. |
| [36] | Chakrabarti S, Visweswariah SS. Intramacrophage ROS primes the innate immune system via JAK/STAT and Toll activation. Cell Rep, 2020, 33(6): 108368. |
| [37] | Jiang HQ, Patel PH, Kohlmaier A, Grenley MO, McEwen DG, Edgar BA. Cytokine/JAK/STAT signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell, 2009, 137(7): 1343-1355. |
| [38] | Buchon N, Broderick NA, Kuraishi T, Lemaitre B. Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection. BMC Biol, 2010, 8: 152. |
| [39] | Sadekuzzaman M, Stanley D, Kim Y. Nitric oxide mediates insect cellular immunity via phospholipase A2 activation. J Innate Immun, 2018, 10(1): 70-81. |
| [40] | Yang L, Qiu LM, Fang Q, Stanley DW, Ye GY. Cellular and humoral immune interactions between Drosophila and its parasitoids. Insect Sci, 2021, 28(5): 1208-1227. |
| [41] | Rodrigues D, Renaud Y, VijayRaghavan K, Waltzer L, Inamdar MS. Differential activation of JAK-STAT signaling reveals functional compartmentalization in Drosophila blood progenitors. Elife, 2021, 10: e61409. |
| [42] | Souza-Neto JA, Sim S, Dimopoulos G. An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense. Proc Natl Acad Sci USA, 2009, 106(42): 17841-17846. |
| [43] | Harsh S, Fu Y, Kenney E, Han Z, Eleftherianos I. Zika virus non-structural protein NS4A restricts eye growth in Drosophila through regulation of JAK/STAT signaling. Dis Model Mech, 2020, 13(4): dmm040816. |
| [44] | Cardoso-Jaime V, Tikhe CV, Dong SZ, Dimopoulos G. The role of mosquito hemocytes in viral infections. Viruses, 2022, 14(10): 2088. |
| [45] | Wang C, Guo XJ, Li YQ, Zhang JZ, Fu YJ. miR-34-5p, encoded by Spodoptera frugiperda, participates in anti-baculovirus by regulating innate immunity in the insect host. Int J Biol Macromol, 2022, 222(Pt B):2190-2199. |
| [46] | Shang Q, Wu P, Huang HL, Zhang SL, Tang XD, Guo XJ.Inhibition of heat shock protein 90 suppresses Bombyx mori nucleopolyhedrovirus replication in B. mori. Insect Mol Biol, 2020, 29(2): 205-213. |
| [47] | Wang YM, He YZ, Ye XT, Guo T, Pan LL, Liu SS, Ng JCK, Wang XW. A balance between vector survival and virus transmission is achieved through JAK/STAT signaling inhibition by a plant virus. Proc Natl Acad Sci USA, 2022, 119(41): e2122099119. |
| [48] | Jupatanakul N, Sim S, Angleró-Rodríguez YI, Souza-Neto J, Das S, Poti KE, Rossi SL, Bergren N, Vasilakis N, Dimopoulos G. Engineered Aedes aegypti JAK/STAT pathway-mediated immunity to dengue virus. PLoS Negl Trop Dis, 2017, 11(1): e0005187. |
| [49] | Xia XF, Yu LY, Xue MQ, Yu XQ, Vasseur L, Gurr GM, Baxter SW, Lin HL, Lin JH, You MS. Genome- wide characterization and expression profiling of immune genes in the diamondback moth, Plutella xylostella (L.). Sci Rep, 2015, 5: 9877. |
| [50] | Ahlers LRH, Trammell CE, Carrell GF, Mackinnon S, Torrevillas BK, Chow CY, Luckhart S, Goodman AG. Insulin potentiates JAK/STAT signaling to broadly inhibit flavivirus replication in insect vectors. Cell Rep, 2019, 29(7): 1946-1960.e5. |
| [51] | Carpenter J, Hutter S, Baines JF, Roller J, Saminadin- Peter SS, Parsch J, Jiggins FM. The transcriptional response of Drosophila melanogaster to infection with the sigma virus (Rhabdoviridae). PLoS One, 2009, 4(8): e6838. |
| [52] | Geng T, Lv DD, Huang YX, Hou CX, Qin GX, Guo XJ. JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana. Gene, 2016, 595(1): 69-76. |
| [53] | Geng T, Lu F, Wu H, Lou D, Tu N, Zhu F, Wang S. Target antifungal peptides of immune signalling pathways in silkworm, Bombyx mori, against Beauveria bassiana. Insect Mol Biol, 2021, 30(1): 102-112. |
/
| 〈 |
|
〉 |
www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:
