PDE4A
PDE4A| PDE4A | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| 식별자 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| 에일리어스 | PDE4A, DPDE2, PDE4, PDE46, 포스포디에스테라아제4A | ||||||||||||||||||||||||||||||||||||||||||||||||||
| 외부 ID | OMIM: 600126 MGI: 99558 HomoloGene: 4520 GeneCard: PDE4A | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| 위키데이터 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
cAMP 특이적 3', 5'-사이클 포스포디에스테라아제 4A는 PDE4A [5][6]유전자에 의해 인체 내에서 코드되는 효소이다.
기능.
이 유전자에 의해 코드된 단백질은 순환 뉴클레오티드 포스포디에스테라아제(PDE) 패밀리 및 PDE4 서브패밀리에 속합니다.이 PDE는 2차 전달자인 cAMP를 가수분해하는데, cAMP는 세포외 신호에 대한 많은 세포 반응의 조절자 및 매개자이다.따라서, cAMP의 세포 농도를 조절함으로써, 이 단백질은 많은 중요한 생리적 [6]과정에서 중요한 역할을 한다.최근에는 PDE4A가 불안과 감정기억 [7]조절에 역할을 할 수 있다는 사실이 PDE4A 녹아웃 마우스를 통해 밝혀졌다.
임상적 의의
PDE4A는 다음을 포함한 [8][9][10]여러 약물의 대상이다.
- 롤립람(항우울제 및 항염증제) 및 실로밀라스트(항염증제)– PDE4A 아이소폼 1, 2, 6, 7을 억제합니다.
- roflumilast(항염증성)– PDE4A 아이소폼 1, 2, 6
레퍼런스
- ^ a b c GRCh38: 앙상블 릴리즈 89: ENSG000065989 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리즈 89: ENSMUSG000032177 - 앙상블, 2017년 5월
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Milatovich A, Bolger G, Michaeli T, Francke U (Mar 1994). "Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse". Somatic Cell and Molecular Genetics. 20 (2): 75–86. doi:10.1007/BF02290677. PMID 8009369. S2CID 19182571.
- ^ a b "PDE4A phosphodiesterase 4A, cAMP-specific ( Homo sapiens )". Entrez Gene. 2012-03-04. Retrieved 2012-04-02.
- ^ Hansen RT, Conti M, Zhang H-T (2014). "Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior". Psychopharmacology. 231 (15): 2941–2954. doi:10.1007/s00213-014-3480-y. PMID 24563185. S2CID 13542300.
- ^ Rena G, Begg F, Ross A, MacKenzie C, McPhee I, Campbell L, Huston E, Sullivan M, Houslay MD (May 2001). "Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10" (PDF). Molecular Pharmacology. 59 (5): 996–1011. doi:10.1124/mol.59.5.996. PMID 11306681.
- ^ Wallace DA, Johnston LA, Huston E, MacMaster D, Houslay TM, Cheung YF, Campbell L, Millen JE, Smith RA, Gall I, Knowles RG, Sullivan M, Houslay MD (Jun 2005). "Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene". Molecular Pharmacology. 67 (6): 1920–34. doi:10.1124/mol.104.009423. PMID 15738310. S2CID 1758221.
- ^ Mackenzie KF, Topping EC, Bugaj-Gaweda B, Deng C, Cheung YF, Olsen AE, Stockard CR, High Mitchell L, Baillie GS, Grizzle WE, De Vivo M, Houslay MD, Wang D, Bolger GB (Apr 2008). "Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that has undergone rapid evolutionary change". The Biochemical Journal. 411 (2): 361–9. doi:10.1042/BJ20071251. PMC 4337886. PMID 18095939.
추가 정보
- Houslay MD, Schafer P, Zhang KY (Nov 2005). "Keynote review: phosphodiesterase-4 as a therapeutic target". Drug Discovery Today. 10 (22): 1503–19. doi:10.1016/S1359-6446(05)03622-6. PMID 16257373.
- Zhang KY, Ibrahim PN, Gillette S, Bollag G (Dec 2005). "Phosphodiesterase-4 as a potential drug target". Expert Opinion on Therapeutic Targets. 9 (6): 1283–305. doi:10.1517/14728222.9.6.1283. PMID 16300476. S2CID 46276184.
- Livi GP, Kmetz P, McHale MM, Cieslinski LB, Sathe GM, Taylor DP, Davis RL, Torphy TJ, Balcarek JM (Jun 1990). "Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase". Molecular and Cellular Biology. 10 (6): 2678–86. doi:10.1128/MCB.10.6.2678. PMC 360627. PMID 2160582.
- Horton YM, Sullivan M, Houslay MD (Jun 1995). "Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19 [corrected]" (PDF). The Biochemical Journal. 308 (2): 683–91. doi:10.1042/bj3080683. PMC 1136980. PMID 7772058.
- Sullivan M, Egerton M, Shakur Y, Marquardsen A, Houslay MD (Sep 1994). "Molecular cloning and expression, in both COS-1 cells and S. cerevisiae, of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1)". Cellular Signalling. 6 (7): 793–812. doi:10.1016/0898-6568(94)00039-5. PMID 7888306.
- Bolger G, Michaeli T, Martins T, St John T, Steiner B, Rodgers L, Riggs M, Wigler M, Ferguson K (Oct 1993). "A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs". Molecular and Cellular Biology. 13 (10): 6558–71. doi:10.1128/mcb.13.10.6558. PMC 364715. PMID 8413254.
- Huston E, Pooley L, Julien P, Scotland G, McPhee I, Sullivan M, Bolger G, Houslay MD (Dec 1996). "The human cyclic AMP-specific phosphodiesterase PDE-46 (HSPDE4A4B) expressed in transfected COS7 cells occurs as both particulate and cytosolic species that exhibit distinct kinetics of inhibition by the antidepressant rolipram" (PDF). The Journal of Biological Chemistry. 271 (49): 31334–44. doi:10.1074/jbc.271.49.31334. PMID 8940140. S2CID 25157712.
- Sullivan M, Rena G, Begg F, Gordon L, Olsen AS, Houslay MD (Aug 1998). "Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2". The Biochemical Journal. 333 (3): 693–703. doi:10.1042/bj3330693. PMC 1219634. PMID 9677330.
- McPhee I, Yarwood SJ, Scotland G, Huston E, Beard MB, Ross AH, Houslay ES, Houslay MD (Apr 1999). "Association with the SRC family tyrosyl kinase LYN triggers a conformational change in the catalytic region of human cAMP-specific phosphodiesterase HSPDE4A4B. Consequences for rolipram inhibition" (PDF). The Journal of Biological Chemistry. 274 (17): 11796–810. doi:10.1074/jbc.274.17.11796. PMID 10206997. S2CID 42776400.
- Zhou L, Thompson WJ, Potter DE (Jul 1999). "Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells" (PDF). Investigative Ophthalmology & Visual Science. 40 (8): 1745–52. PMID 10393044.
- Secchiero P, Zella D, Curreli S, Mirandola P, Capitani S, Gallo RC, Zauli G (Dec 2000). "Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication". Proceedings of the National Academy of Sciences of the United States of America. 97 (26): 14620–5. doi:10.1073/pnas.011512398. PMC 18968. PMID 11114167.
- Zauli G, Milani D, Mirandola P, Mazzoni M, Secchiero P, Miscia S, Capitani S (Feb 2001). "HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway" (PDF). FASEB Journal. 15 (2): 483–91. doi:10.1096/fj.00-0354com. PMID 11156964. S2CID 26315564.
- Lario PI, Bobechko B, Bateman K, Kelly J, Vrielink A, Huang Z (Oct 2001). "Purification and characterization of the human PDE4A catalytic domain (PDE4A330-723) expressed in Sf9 cells". Archives of Biochemistry and Biophysics. 394 (1): 54–60. doi:10.1006/abbi.2001.2513. PMID 11566027.
- Moon E, Lee R, Near R, Weintraub L, Wolda S, Lerner A (Feb 2002). "Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia" (PDF). Clinical Cancer Research. 8 (2): 589–95. PMID 11839681.
- Laliberté F, Liu S, Gorseth E, Bobechko B, Bartlett A, Lario P, Gresser MJ, Huang Z (Feb 2002). "In vitro PKA phosphorylation-mediated human PDE4A4 activation". FEBS Letters. 512 (1–3): 205–8. doi:10.1016/S0014-5793(02)02259-7. PMID 11852080. S2CID 27637592.
- Baillie GS, Huston E, Scotland G, Hodgkin M, Gall I, Peden AH, MacKenzie C, Houslay ES, Currie R, Pettitt TR, Walmsley AR, Wakelam MJ, Warwicker J, Houslay MD (Aug 2002). "TAPAS-1, a novel microdomain within the unique N-terminal region of the PDE4A1 cAMP-specific phosphodiesterase that allows rapid, Ca2+-triggered membrane association with selectivity for interaction with phosphatidic acid" (PDF). The Journal of Biological Chemistry. 277 (31): 28298–309. doi:10.1074/jbc.M108353200. PMID 11994273. S2CID 21243391.
- Pryzwansky KB, Madden VJ (Jun 2003). "Type 4A cAMP-specific phosphodiesterase is stored in granules of human neutrophils and eosinophils". Cell and Tissue Research. 312 (3): 301–11. doi:10.1007/s00441-003-0728-y. PMID 12764607. S2CID 8501967.
PDB 갤러리 | |
|---|---|
|
