대식량 이동 억제 인자

Macrophage migration inhibitory factor
MIF
Protein MIF PDB 1ca7.png
사용 가능한 구조물
PDB직교 검색: PDBe RCSB
식별자
별칭MIF, GIF, GLIF, mmacropage 마이그레이션 억제 인자(글리코실레이션-억제 인자), 대식량 마이그레이션 억제 인자
외부 IDOMIM: 153620 MGI: 96982 HomoloGene: 55655 GeneCard: MIF
EC 번호5.3.3.12
직교체
종인간마우스
엔트레스

4282

17319

앙상블

ENSG00000276701
ENSG00000240972

ENSMUSG00000033307

유니프로트

P14174

P34884

RefSeq(mRNA)

NM_002415

NM_010798

RefSeq(단백질)

NP_002406
NP_002406.1

NP_034928

위치(UCSC)Cr 22: 23.89 – 23.9MbChr 10: 75.7 – 75.7Mb
PubMed 검색[3][4]
위키다타
인간 보기/편집마우스 보기/편집
대식량 마이그레이션 억제 인자(MIF)
식별자
기호MIF
PfamPF01187
인터프로IPR001398
프로사이트PDOC00892
SCOP21mif / SCOPe / SUPFAM

대식세포이동억제인자(MIF), L-도파크롬 이소머라아제 또는 페닐피루베이트 tautomerase라고도 알려진 대식세포이동억제인자(MIF)는 인간에서 MIF 유전자에 의해 인코딩되는 단백질이다.[5][6]MIF는 선천적 면역의 중요한 조절기다.[7]MIF 단백질 슈퍼 패밀리는 기능적으로 관련된 성질을 가진 두 번째 멤버인 D-도파크롬 tautomerase(D-DT)도 포함한다.[8]CD74는 MIF의 표면 수용체다.[9]

박테리아 항원은 백혈구를 자극하여 MIF를 혈류로 방출한다.[10]순환 MIF는 다른 면역세포의 CD74와 결합하여 급성 면역반응을 일으킨다.따라서 MIF는 염증성 사이토카인으로 분류된다.게다가 글루코코르티코이드들은 또한 백혈구를 자극하여 MIF를 방출하고 따라서 MIF는 부분적으로 글루코코르티코이드들이 면역체계에 미치는 억제 효과를 상쇄시킨다.마지막으로 외상은 전방 뇌하수체를 활성화하여 MIF를 방출한다.[11]

구조

대식세포 이동 억제 인자는 동일한 세 개의 하위 유니트로 구성된 트리머로 조립된다.각각의 모노머에는 2개의 대타렐 알파 나선과 4개의 줄무늬 베타 시트가 들어 있다.모노머는 중심 채널을 3배 회전 대칭으로 둘러싸고 있다.[12][13]

부상에 대한 대응

사이토카인은 상처 치유와 조직 회복을 촉진하는 데 중요한 역할을 한다.세포 부상은 MIF 방출로 이어 CD74와 상호작용한다. MIF-CD74 신호는 부상 중 숙주를 보호하는 생존 및 증식 경로를 활성화한다.[14]

효소 활성

MIF에는 촉매 활성의 두 가지 모티브가 포함되어 있다.첫 번째는 N-terminus에 위치한 27개의 아미노산 모티브로 2-카르복시-2,3-디하이드록신돌-5,6-퀴논(도파크롬)을 5,6-디하이드록신돌-2-카르복시산(DHICA)으로 변환하는 촉매제 역할을 할 수 있는 페닐피루브레이트 토토머레이즈다.[15][16]MIF는 또한 이황화 환원제로 기능하는 것으로 보이는 잔류물 57과 60 사이의 Cys-Ala-Leu-Cys 촉매 부지를 포함한다.[17]

함수

이 유전자는 세포 매개 면역, 면역억제, 염증 등과 관련된 림프구를 암호화한다.[18][19][20]MIF는 글루코르티코이드의 항염증 효과 억제를 통해 호스트 방어에서 대식세포 기능을 규제하는 역할을 한다.[20][21][22]이 림포킨과 JAB1 단백질은 말초 혈장막 근처의 세포솔에서 복합체를 형성하며, 이것은 통합 신호 경로의 역할을 나타낼 수 있다.[23]

작용기전

MIF는 CD74에 바인딩되어 [24]인산염과 CD44의 모집을 유도하여 비수용체 타이로신 키나제를 활성화하여 궁극적으로 세포외 신호 조절 키나제 인산염으로 이어진다.[25]ERK 외에도 CD74 자극은 PI3K-Akt, NF-164B, AMP-활성 단백질 키나아제(AMPK) 경로와 같은 다른 신호 경로를 활성화한다.[26]

상호작용

대식세포 마이그레이션 억제 요인은 다음과 상호작용하는 것으로 보고되었다.

임상적 유의성

MIF는 패혈증, 류마티스 관절염, 암의 잠재적인 약물 목표물이다.[40][41]

기생충 생산 MIF 호몰로고

면역 회피, 침입, 병태생성에서의 기생충 생산 MIF 사이토카인

복수의 원생동물 기생충은 인간 MIF와 유사한 염증 기능을 가진 동질성 MIF를 생성하며, 이들의 병원성, 침입, 면역 회피에 역할을 한다.[42][43]한 임상 전 연구는 기생충 MIF를 차단하는 것이 심각한 원생동물 감염에서 결과를 향상시킨다는 것을 보여주었다.[44]보고된 MIF 호몰로지를 가진 원생대의 예:

참조

  1. ^ a b c ENSG00000240972 GRCh38: 앙상블 릴리스 89: ENSG00000276701, ENSG00000240972 - 앙상블, 2017년 5월
  2. ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG00000033307 - 앙상블, 2017년 5월
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Weiser WY, Temple PA, Witek-Giannotti JS, Remold HG, Clark SC, David JR (October 1989). "Molecular cloning of a cDNA encoding a human macrophage migration inhibitory factor". Proceedings of the National Academy of Sciences of the United States of America. 86 (19): 7522–6. Bibcode:1989PNAS...86.7522W. doi:10.1073/pnas.86.19.7522. PMC 298097. PMID 2552447.
  6. ^ Kozak CA, Adamson MC, Buckler CE, Segovia L, Paralkar V, Wistow G (June 1995). "Genomic cloning of mouse MIF (macrophage inhibitory factor) and genetic mapping of the human and mouse expressed gene and nine mouse pseudogenes". Genomics. 27 (3): 405–11. doi:10.1006/geno.1995.1070. PMID 7558020.
  7. ^ Calandra T, Roger T (October 2003). "Macrophage migration inhibitory factor: a regulator of innate immunity". Nature Reviews. Immunology. 3 (10): 791–800. doi:10.1038/nri1200. PMC 7097468. PMID 14502271.
  8. ^ Günther S, Fagone P, Jalce G, Atanasov AG, Guignabert C, Nicoletti F (February 2019). "Role of MIF and D-DT in immune-inflammatory, autoimmune, and chronic respiratory diseases: from pathogenic factors to therapeutic targets". Drug Discovery Today. 24 (2): 428–439. doi:10.1016/j.drudis.2018.11.003. PMID 30439447.
  9. ^ Farr L, Ghosh S, Moonah S (2020). "Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair". Frontiers in Immunology. 11: 1273. doi:10.3389/fimmu.2020.01273. PMC 7325688. PMID 32655566.
  10. ^ Barret, James (1980). Basic Immunology and its Medical Application (2 ed.). St.Louis: The C.V. Mosby Company. ISBN 978-0-8016-0495-9.
  11. ^ Larson DF, Horak K (2006). "Macrophage migration inhibitory factor: controller of systemic inflammation". Critical Care. 10 (2): 138. doi:10.1186/cc4899. PMC 1550887. PMID 16677407.
  12. ^ Sun HW, Bernhagen J, Bucala R, Lolis E (May 1996). "Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor". Proceedings of the National Academy of Sciences of the United States of America. 93 (11): 5191–6. doi:10.1073/pnas.93.11.5191. PMC 39220. PMID 8643551.
  13. ^ Al-Abed Y, VanPatten S (January 2011). "MIF as a disease target: ISO-1 as a proof-of-concept therapeutic". Future Medicinal Chemistry. 3 (1): 45–63. doi:10.4155/fmc.10.281. PMID 21428825.
  14. ^ Farr L, Ghosh S, Moonah S (2020). "Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair". Frontiers in Immunology. 11: 1273. doi:10.3389/fimmu.2020.01273. PMC 7325688. PMID 32655566.
  15. ^ Rosengren E, Bucala R, Aman P, Jacobsson L, Odh G, Metz CN, Rorsman H (January 1996). "The immunoregulatory mediator macrophage migration inhibitory factor (MIF) catalyzes a tautomerization reaction". Molecular Medicine. 2 (1): 143–9. doi:10.1007/BF03402210. PMC 2230029. PMID 8900542.
  16. ^ Veillat V, Carli C, Metz CN, Al-Abed Y, Naccache PH, Akoum A (December 2010). "Macrophage migration inhibitory factor elicits an angiogenic phenotype in human ectopic endometrial cells and triggers the production of major angiogenic factors via CD44, CD74, and MAPK signaling pathways". The Journal of Clinical Endocrinology and Metabolism. 95 (12): E403-12. doi:10.1210/jc.2010-0417. PMID 20829186.
  17. ^ Thiele M, Bernhagen J (2005). "Link between macrophage migration inhibitory factor and cellular redox regulation". Antioxidants & Redox Signaling. 7 (9–10): 1234–48. doi:10.1089/ars.2005.7.1234. PMID 16115028.
  18. ^ Leng L, Bucala R (February 2006). "Insight into the biology of macrophage migration inhibitory factor (MIF) revealed by the cloning of its cell surface receptor". Cell Research. 16 (2): 162–8. doi:10.1038/sj.cr.7310022. PMID 16474429.
  19. ^ Chen PF, Luo YL, Wang W, Wang JX, Lai WY, Hu SM, et al. (2010). "ISO-1, a macrophage migration inhibitory factor antagonist, inhibits airway remodeling in a murine model of chronic asthma". Molecular Medicine. 16 (9–10): 400–8. doi:10.2119/molmed.2009.00128. PMC 2935952. PMID 20485865.
  20. ^ a b Takahashi K, Koga K, Linge HM, Zhang Y, Lin X, Metz CN, et al. (May 2009). "Macrophage CD74 contributes to MIF-induced pulmonary inflammation". Respiratory Research. 10 (1): 33. doi:10.1186/1465-9921-10-33. PMC 2681459. PMID 19413900.
  21. ^ Flaster H, Bernhagen J, Calandra T, Bucala R (June 2007). "The macrophage migration inhibitory factor-glucocorticoid dyad: regulation of inflammation and immunity". Molecular Endocrinology. 21 (6): 1267–80. doi:10.1210/me.2007-0065. PMID 17389748.
  22. ^ Al-Abed Y, Metz CN, Cheng KF, Aljabari B, VanPatten S, Blau S, et al. (May 2011). "Thyroxine is a potential endogenous antagonist of macrophage migration inhibitory factor (MIF) activity". Proceedings of the National Academy of Sciences of the United States of America. 108 (20): 8224–7. Bibcode:2011PNAS..108.8224A. doi:10.1073/pnas.1017624108. PMC 3100930. PMID 21536912.
  23. ^ "Entrez Gene: MIF macrophage migration inhibitory factor (glycosylation-inhibiting factor)".
  24. ^ Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, et al. (October 1993). "MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia". Nature. 365 (6448): 756–9. Bibcode:1993Natur.365..756B. doi:10.1038/365756a0. PMID 8413654. S2CID 4321353.
  25. ^ Shi X, Leng L, Wang T, Wang W, Du X, Li J, et al. (October 2006). "CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex". Immunity. 25 (4): 595–606. doi:10.1016/j.immuni.2006.08.020. PMC 3707630. PMID 17045821.
  26. ^ Farr L, Ghosh S, Moonah S (2020). "Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair". Frontiers in Immunology. 11: 1273. doi:10.3389/fimmu.2020.01273. PMC 7325688. PMID 32655566.
  27. ^ Shen L, Hu J, Lu H, Wu M, Qin W, Wan D, et al. (April 2003). "The apoptosis-associated protein BNIPL interacts with two cell proliferation-related proteins, MIF and GFER". FEBS Letters. 540 (1–3): 86–90. doi:10.1016/S0014-5793(03)00229-1. PMID 12681488.
  28. ^ Farr L, Ghosh S, Jiang N, Watanabe K, Parlak M, Bucala R, Moonah S (2020). "CD74 Signaling Links Inflammation to Intestinal Epithelial Cell Regeneration and Promotes Mucosal Healing". Cellular and Molecular Gastroenterology and Hepatology. 10 (1): 101–112. doi:10.1016/j.jcmgh.2020.01.009. PMC 7215244. PMID 32004754.
  29. ^ Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, et al. (June 2003). "MIF signal transduction initiated by binding to CD74". The Journal of Experimental Medicine. 197 (11): 1467–76. doi:10.1084/jem.20030286. PMC 2193907. PMID 12782713.
  30. ^ Bacher M, Deuster O, Aljabari B, Egensperger R, Neff F, Jessen F, et al. (March 2010). "The role of macrophage migration inhibitory factor in Alzheimer's disease". Molecular Medicine. 16 (3–4): 116–21. doi:10.2119/molmed.2009.00123. PMC 2829616. PMID 20200619.
  31. ^ Shan ZX, Lin QX, Deng CY, Tan HH, Kuang SJ, Xiao DZ, et al. (December 2009). "[Identification of the interactions between the truncated fragments of macrophage migration inhibitory factor and CD74 using a yeast two-hybrid system]". Nan Fang Yi Ke da Xue Xue Bao = Journal of Southern Medical University (in Chinese). 29 (12): 2383–6, 2390. PMID 20034881.
  32. ^ Wang F, Shen X, Guo X, Peng Y, Liu Y, Xu S, Yang J (February 2010). "Spinal macrophage migration inhibitory factor contributes to the pathogenesis of inflammatory hyperalgesia in rats". Pain. 148 (2): 275–83. doi:10.1016/j.pain.2009.11.011. PMID 20005040. S2CID 38141283.
  33. ^ Dobson SE, Augustijn KD, Brannigan JA, Schnick C, Janse CJ, Dodson EJ, et al. (December 2009). "The crystal structures of macrophage migration inhibitory factor from Plasmodium falciparum and Plasmodium berghei". Protein Science. 18 (12): 2578–91. doi:10.1002/pro.263. PMC 2798171. PMID 19827093.
  34. ^ Ghosh S, Leaton LA, Farr L, Barfield A, Moonah S (July 2018). "Interaction between parasite-encoded JAB1/CSN5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function". Scientific Reports. 8 (1): 10241. Bibcode:2018NatSR...810241G. doi:10.1038/s41598-018-28625-1. PMC 6035221. PMID 29980718.
  35. ^ Kleemann R, Hausser A, Geiger G, Mischke R, Burger-Kentischer A, Flieger O, et al. (November 2000). "Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1". Nature. 408 (6809): 211–6. Bibcode:2000Natur.408..211K. doi:10.1038/35041591. PMID 11089976. S2CID 205010648.
  36. ^ Schwartz V, Lue H, Kraemer S, Korbiel J, Krohn R, Ohl K, et al. (September 2009). "A functional heteromeric MIF receptor formed by CD74 and CXCR4". FEBS Letters. 583 (17): 2749–57. doi:10.1016/j.febslet.2009.07.058. PMC 2911026. PMID 19665027.
  37. ^ Schrader J, Deuster O, Rinn B, Schulz M, Kautz A, Dodel R, et al. (December 2009). "Restoration of contact inhibition in human glioblastoma cell lines after MIF knockdown". BMC Cancer. 9: 464. doi:10.1186/1471-2407-9-464. PMC 2810303. PMID 20038293.
  38. ^ Stosic-Grujicic S, Stojanovic I, Maksimovic-Ivanic D, Momcilovic M, Popadic D, Harhaji L, et al. (June 2008). "Macrophage migration inhibitory factor (MIF) is necessary for progression of autoimmune diabetes mellitus". Journal of Cellular Physiology. 215 (3): 665–75. doi:10.1002/jcp.21346. PMID 18064633. S2CID 36047003.
  39. ^ Filip AM, Klug J, Cayli S, Fröhlich S, Henke T, Lacher P, et al. (March 2009). "Ribosomal protein S19 interacts with macrophage migration inhibitory factor and attenuates its pro-inflammatory function". The Journal of Biological Chemistry. 284 (12): 7977–85. doi:10.1074/jbc.M808620200. PMC 2658091. PMID 19155217.
  40. ^ Lue H, Kleemann R, Calandra T, Roger T, Bernhagen J (April 2002). "Macrophage migration inhibitory factor (MIF): mechanisms of action and role in disease". Microbes and Infection. 4 (4): 449–60. doi:10.1016/S1286-4579(02)01560-5. PMID 11932196.
  41. ^ Bloom J, Sun S, Al-Abed Y (December 2016). "MIF, a controversial cytokine: a review of structural features, challenges, and opportunities for drug development". Expert Opinion on Therapeutic Targets. 20 (12): 1463–1475. doi:10.1080/14728222.2016.1251582. PMID 27762152. S2CID 36752674.
  42. ^ Ghosh S, Jiang N, Farr L, Ngobeni R, Moonah S (21 August 2019). "Parasite-Produced MIF Cytokine: Role in Immune Evasion, Invasion, and Pathogenesis". Frontiers in Immunology. 10: 1995. doi:10.3389/fimmu.2019.01995. PMC 6712082. PMID 31497025.
  43. ^ Bennett JE, Dolin R, Blaser MJ (2014). Principles and Practice of Infectious Diseases. Elsevier Health Sciences. p. 32. ISBN 9781455748013.
  44. ^ Ghosh S, Padalia J, Ngobeni R, Abendroth J, Farr L, Shirley DA, et al. (March 2020). "Targeting Parasite-Produced Macrophage Migration Inhibitory Factor as an Antivirulence Strategy With Antibiotic-Antibody Combination to Reduce Tissue Damage". The Journal of Infectious Diseases. 221 (7): 1185–1193. doi:10.1093/infdis/jiz579. PMC 7325720. PMID 31677380.
  45. ^ Ngobeni R, Abhyankar MM, Jiang NM, Farr LA, Samie A, Haque R, Moonah SN (April 2017). "Entamoeba histolytica-Encoded Homolog of Macrophage Migration Inhibitory Factor Contributes to Mucosal Inflammation during Amebic Colitis". The Journal of Infectious Diseases. 215 (8): 1294–1302. doi:10.1093/infdis/jix076. PMC 5853319. PMID 28186296.
  46. ^ Sun T, Holowka T, Song Y, Zierow S, Leng L, Chen Y, et al. (July 2012). "A Plasmodium-encoded cytokine suppresses T-cell immunity during malaria". Proceedings of the National Academy of Sciences of the United States of America. 109 (31): E2117-26. doi:10.1073/pnas.1206573109. PMC 3411961. PMID 22778413.
  47. ^ Sommerville C, Richardson JM, Williams RA, Mottram JC, Roberts CW, Alexander J, Henriquez FL (May 2013). "Biochemical and immunological characterization of Toxoplasma gondii macrophage migration inhibitory factor". The Journal of Biological Chemistry. 288 (18): 12733–41. doi:10.1074/jbc.M112.419911. PMC 3642319. PMID 23443656.
  48. ^ Holowka T, Castilho TM, Garcia AB, Sun T, McMahon-Pratt D, Bucala R (June 2016). "Leishmania-encoded orthologs of macrophage migration inhibitory factor regulate host immunity to promote parasite persistence". FASEB Journal. 30 (6): 2249–65. doi:10.1096/fj.201500189R. PMC 4871794. PMID 26956417.
  49. ^ Twu O, Dessí D, Vu A, Mercer F, Stevens GC, de Miguel N, et al. (June 2014). "Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses". Proceedings of the National Academy of Sciences of the United States of America. 111 (22): 8179–84. Bibcode:2014PNAS..111.8179T. doi:10.1073/pnas.1321884111. PMC 4050605. PMID 24843155.

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