PPP1R1B
PPP1R1B| PPP1R1B | |||||||||||||||||||||||||
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| 에일리어스 | PPP1R1B, DARPP-32, DARPP32, 단백질인산가수분해효소1조절억제서브유닛1B | ||||||||||||||||||||||||
| 외부 ID | OMIM: 604399 MGI: 94860 HomoloGene: 12972 GenCard: PPP1R1B | ||||||||||||||||||||||||
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| 종. | 인간 | 마우스 | |||||||||||||||||||||||
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| 장소(UCSC) | Chr 17: 39.63 ~39.64 Mb | Chr 11: 98.24 ~98.25 Mb | |||||||||||||||||||||||
| PubMed 검색 | [3] | [4] | |||||||||||||||||||||||
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도파민 및 cAMP 조절 신경인산단백질(DARPP-32)이라고도 알려진 단백질 포스파타아제 1 조절 서브유닛 1B(PPP1R1B)는 사람에게서 PPP1R1B [5][6]유전자에 의해 암호화되는 단백질이다.
기능.
중뇌 도파민 신경 세포는 다발성 뇌 기능에 중요한 역할을 하며 도파민 신경 경로를 통한 비정상적인 신호 전달은 몇몇 주요 신경 및 정신 질환과 관련이 있다.도파민의 작용에 대해 잘 연구된 표적 중 하나는 DARPP32이다.DARPP32는 도파민 D1 [8]수용체를 발현하는 중간 크기의 가시 뉴런에서[7] 발현된다.DARPP32의 기능은 수용체 자극에 의해 조절되는 것으로 보입니다.도파민 작동성 수용체와 글루탐산 수용체(NMDA) 수용체 자극은 모두 DARPP32 인산화 정도를 조절하지만 반대 방향으로 [9]조절한다.도파민 D1 수용체 자극은 cAMP [8]형성을 촉진하여 DARPP32의 인산화를 초래한다. (이는 cAMP 시그널링이 DARPP32의[10] 탈인산화를 유도한다는 보다 최근의 연구에 의해 논쟁된다.) 인산화 DARPP32는 강력한 단백질 포스파타아제-1([11]PP1CA) 억제제이다.NMDA수용체 자극 여기는 칼시뉴린과 phospho-DARPP32의 dephosphorylation의 활성화로 이어진다 세포 내 칼슘,, DARPP32의phosphatase-1 억제 활동을 줄이는 방법이다.[5][9]DARPP-32 도파민 종속striatal하고 있는 시냅스 plasticity,[12]에 아마 ca.을 위한dopamine-dependent gating 메커니즘의 작용을 함으로써 중요하다lcium/CaMKII [13]시그널링DARPP-32는 ARPP-21과 함께 선조체 시냅스 후 [13]시그널링을 위한 적격 추적과 같은 시간창 설정에도 관여할 수 있을 것으로 예측되고 있다.
임상적 의의
CNS
이 유전자는 DARPP-32로도 알려져 도파민 및 고리형 AMP 조절 인단백질으로서의 역할을 강조한다.이와 같이 PPP1R1B는 도파민,[14] 글루탐산 및 아데노신에 영향을 미치며, 정신분열증에서의 유전자 역할뿐만 아니라 코카인, 암페타민, 니코틴, LSD, 카페인, PCP, 에탄올 [15]및 모르핀을 포함한 약물 작용과 파킨슨병 또는 EPS(피라미달외 증상)[16]에 관여한다.DARPP-32 수치는 정신분열증 [17][18][19]및 조울증 환자 모두의 배측 전전두피질 및 림프구에서 감소한다.항정신병 약물들은 DARPP-32의 [20][21]발현을 조절하지 않기 때문에 이러한 변화는 병리학과 관련이 있는 것으로 제안된다.
DARPP-32의 PKA의존적 인산화 및 아데노신 A2A [22]전달을 통해 달성되는 선조체 투영 뉴런의 신호 캐스케이드에 의해 칸나비노이드의 상당한 비율을 설명할 수 있다.
PPP1R1B는 선조체와 전전두엽 피질 사이의 정보 전달 개선과도 관련이 있으며, 이는 PPP1R1B의 변종이 어떤 상황에서는 개선되고 보다 유연한 인식으로 이어질 수 있는 반면, 다른 유전적 및 환경적 요인이 존재하는 경우에는 정신 분열증 [23]증상으로 이어질 수 있음을 시사한다.
암
PPP1R1B에 의해 암호화되는 단백질 생성물은 DARPP-32와 t-Darpp 두 가지가 있다.t-Darpp는 DARPP-32의 잘린 버전이며,[24] N 말단에는 최초의 36개의 아미노산이 없기 때문이다.위,[25][26] 대장, 전립선, 식도, 유방 및 폐 조직에서 파생된 암을 포함한 많은 암에서 두 등소형 모두 과다 발현된다.Her-2 양성 유방암 세포에서 t-Darpp 과발현은 Her-2 [27][28][29]시그널링 경로를 차단하는 화학요법 약물인 Trastuzumab(Herceptin)에 내성을 부여한다.
규정
뇌유래 신경영양인자는 DARPP-32의 [30]발현을 조절한다.Akt와 CDK5/p35의 쇄골내 경로가 이 [31]규정에 관여하는 것이 권장된다.또한 DARPP-32의 [32]발현을 조절하기 위해 신경 칼슘 센서-1이 제안되었다.
검출
PPP1R1B는 Paul Greengard와 그의 [6]동료들에 의해 발견되었습니다.
인터랙티브 패스 맵
아래의 유전자, 단백질 및 대사물을 클릭하여 각각의 기사와 연결하세요.[§ 1]
도파민성 뉴런의 니코틴 활성 편집
- ^ 대화형 경로 맵은 WikiPathways에서 편집할 수 있습니다."NicotineDopaminergic_WP1602".
레퍼런스
- ^ a b c GRCh38: 앙상블 릴리즈 89: ENSG00000131771 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리즈 89: ENSMUSG000061718 - 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.
- ^ a b "Entrez Gene: PPP1R1B protein phosphatase 1, regulatory (inhibitor) subunit 1B (dopamine and cAMP regulated phosphoprotein, DARPP-32)".
- ^ a b Brené S, Lindefors N, Ehrlich M, Taubes T, Horiuchi A, Kopp J, Hall H, Sedvall G, Greengard P, Persson H (March 1994). "Expression of mRNAs encoding ARPP-16/19, ARPP-21, and DARPP-32 in human brain tissue". The Journal of Neuroscience. 14 (3 Pt 1): 985–98. doi:10.1523/JNEUROSCI.14-03-00985.1994. PMC 6577526. PMID 8120638.
- ^ Ouimet CC, Greengard P (February 1990). "Distribution of DARPP-32 in the basal ganglia: an electron microscopic study". Journal of Neurocytology. 19 (1): 39–52. doi:10.1007/BF01188438. PMID 2191086. S2CID 33812522.
- ^ a b Walaas SI, Greengard P (January 1984). "DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. I. Regional and cellular distribution in the rat brain". The Journal of Neuroscience. 4 (1): 84–98. doi:10.1523/JNEUROSCI.04-01-00084.1984. PMC 6564747. PMID 6319627.
- ^ a b Halpain S, Girault JA, Greengard P (January 1990). "Activation of NMDA receptors induces dephosphorylation of DARPP-32 in rat striatal slices". Nature. 343 (6256): 369–72. Bibcode:1990Natur.343..369H. doi:10.1038/343369a0. PMID 2153935. S2CID 4319592.
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- ^ Hemmings HC, Greengard P, Tung HY, Cohen P (1984). "DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1". Nature. 310 (5977): 503–5. Bibcode:1984Natur.310..503H. doi:10.1038/310503a0. PMID 6087160. S2CID 4307053.
- ^ Yagishita S, Hayashi-Takagi A, Ellis-Davies GC, Urakubo H, Ishii S, Kasai H (September 2014). "A critical time window for dopamine actions on the structural plasticity of dendritic spines". Science. 345 (6204): 1616–20. Bibcode:2014Sci...345.1616Y. doi:10.1126/science.1255514. PMC 4225776. PMID 25258080.
- ^ a b Nair AG, Bhalla US, Hellgren Kotaleski J (September 2016). "Role of DARPP-32 and ARPP-21 in the Emergence of Temporal Constraints on Striatal Calcium and Dopamine Integration". PLOS Computational Biology. 12 (9): e1005080. Bibcode:2016PLSCB..12E5080N. doi:10.1371/journal.pcbi.1005080. PMC 5008828. PMID 27584878.
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- ^ Svenningsson P, Nairn AC, Greengard P (October 2005). "DARPP-32 mediates the actions of multiple drugs of abuse". The AAPS Journal. 7 (2): E353-60. doi:10.1208/aapsj070235. PMC 2750972. PMID 16353915.
- ^ Clinton SM, Ibrahim HM, Frey KA, Davis KL, Haroutunian V, Meador-Woodruff JH (October 2005). "Dopaminergic abnormalities in select thalamic nuclei in schizophrenia: involvement of the intracellular signal integrating proteins calcyon and spinophilin". The American Journal of Psychiatry. 162 (10): 1859–71. doi:10.1176/appi.ajp.162.10.1859. PMID 16199832.
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- ^ Ishikawa M, Mizukami K, Iwakiri M, Asada T (August 2007). "Immunohistochemical and immunoblot analysis of Dopamine and cyclic AMP-regulated phosphoprotein, relative molecular mass 32,000 (DARPP-32) in the prefrontal cortex of subjects with schizophrenia and bipolar disorder". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 31 (6): 1177–81. doi:10.1016/j.pnpbp.2007.04.013. PMID 17521792. S2CID 27481326.
- ^ Torres KC, Souza BR, Miranda DM, Nicolato R, Neves FS, Barros AG, Dutra WO, Gollob KJ, Correa H, Romano-Silva MA (March 2009). "The leukocytes expressing DARPP-32 are reduced in patients with schizophrenia and bipolar disorder". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 33 (2): 214–9. doi:10.1016/j.pnpbp.2008.10.020. PMID 19059449. S2CID 8431767.
- ^ Souza BR, Motta BS, Rosa DV, Torres KC, Castro AA, Comim CM, Sampaio AM, Lima FF, Jeromin A, Quevedo J, Romano-Silva MA (March 2008). "DARPP-32 and NCS-1 expression is not altered in brains of rats treated with typical or atypical antipsychotics". Neurochemical Research. 33 (3): 533–8. doi:10.1007/s11064-007-9470-2. PMID 17763944. S2CID 27727055.
- ^ Souza BR, Torres KC, Miranda DM, Motta BS, Scotti-Muzzi E, Guimarães MM, Carneiro DS, Rosa DV, Souza RP, Reis HJ, Jeromin A, Romano-Silva MA (June 2010). "Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1". Journal of Negative Results in Biomedicine. 9: 4. doi:10.1186/1477-5751-9-4. PMC 2912242. PMID 20565907.
- ^ Andersson M, Usiello A, Borgkvist A, Pozzi L, Dominguez C, Fienberg AA, Svenningsson P, Fredholm BB, Borrelli E, Greengard P, Fisone G (September 2005). "Cannabinoid action depends on phosphorylation of dopamine- and cAMP-regulated phosphoprotein of 32 kDa at the protein kinase A site in striatal projection neurons". The Journal of Neuroscience. 25 (37): 8432–8. doi:10.1523/JNEUROSCI.1289-05.2005. PMC 6725667. PMID 16162925.
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- ^ El-Rifai W, Smith MF, Li G, Beckler A, Carl VS, Montgomery E, Knuutila S, Moskaluk CA, Frierson HF, Powell SM (July 2002). "Gastric cancers overexpress DARPP-32 and a novel isoform, t-DARPP". Cancer Research. 62 (14): 4061–4. PMID 12124342.
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- ^ Alam SK, Astone M, Liu P, Hall SR, Coyle AM, Dankert EN, Hoffman DK, Zhang W, Kuang R, Roden AC, Mansfield AS, Hoeppner LH (2018-05-03). "DARPP-32 and t-DARPP promote non-small cell lung cancer growth through regulation of IKKα-dependent cell migration". Communications Biology. 1 (1): 43. doi:10.1038/s42003-018-0050-6. PMC 5959014. PMID 29782621.
- ^ Gu L, Waliany S, Kane SE (July 2009). "Darpp-32 and its truncated variant t-Darpp have antagonistic effects on breast cancer cell growth and herceptin resistance". PLOS ONE. 4 (7): e6220. Bibcode:2009PLoSO...4.6220G. doi:10.1371/journal.pone.0006220. PMC 2704867. PMID 19593441.
- ^ Hamel S, Bouchard A, Ferrario C, Hassan S, Aguilar-Mahecha A, Buchanan M, Quenneville L, Miller W, Basik M (February 2010). "Both t-Darpp and DARPP-32 can cause resistance to trastuzumab in breast cancer cells and are frequently expressed in primary breast cancers". Breast Cancer Research and Treatment. 120 (1): 47–57. doi:10.1007/s10549-009-0364-7. PMID 19301121. S2CID 20958252.
- ^ Belkhiri A, Dar AA, Peng DF, Razvi MH, Rinehart C, Arteaga CL, El-Rifai W (July 2008). "Expression of t-DARPP mediates trastuzumab resistance in breast cancer cells". Clinical Cancer Research. 14 (14): 4564–71. doi:10.1158/1078-0432.CCR-08-0121. PMC 2842884. PMID 18579663.
- ^ Stroppolo A, Guinea B, Tian C, Sommer J, Ehrlich ME (December 2001). "Role of phosphatidylinositide 3-kinase in brain-derived neurotrophic factor-induced DARPP-32 expression in medium size spiny neurons in vitro". Journal of Neurochemistry. 79 (5): 1027–32. doi:10.1046/j.1471-4159.2001.00651.x. PMID 11739615. S2CID 35861963.
- ^ Bogush A, Pedrini S, Pelta-Heller J, Chan T, Yang Q, Mao Z, Sluzas E, Gieringer T, Ehrlich ME (March 2007). "AKT and CDK5/p35 mediate brain-derived neurotrophic factor induction of DARPP-32 in medium size spiny neurons in vitro". The Journal of Biological Chemistry. 282 (10): 7352–9. doi:10.1074/jbc.M606508200. PMID 17209049.
- ^ Souza BR, Torres KC, Miranda DM, Motta BS, Caetano FS, Rosa DV, Souza RP, Giovani A, Carneiro DS, Guimarães MM, Martins-Silva C, Reis HJ, Gomez MV, Jeromin A, Romano-Silva MA (January 2011). "Downregulation of the cAMP/PKA pathway in PC12 cells overexpressing NCS-1". Cellular and Molecular Neurobiology. 31 (1): 135–43. doi:10.1007/s10571-010-9562-4. PMID 20838877. S2CID 25500946.
추가 정보
- Hemmings HC, Nairn AC, Greengard P (December 1984). "DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated neuronal phosphoprotein. II. Comparison of the kinetics of phosphorylation of DARPP-32 and phosphatase inhibitor 1". The Journal of Biological Chemistry. 259 (23): 14491–7. doi:10.1016/S0021-9258(17)42626-3. PMID 6501303.
- Zachariou V, Sgambato-Faure V, Sasaki T, Svenningsson P, Berton O, Fienberg AA, Nairn AC, Greengard P, Nestler EJ (March 2006). "Phosphorylation of DARPP-32 at Threonine-34 is required for cocaine action". Neuropsychopharmacology. 31 (3): 555–62. doi:10.1038/sj.npp.1300832. PMID 16123776.
- Rosack, J (20 September 2002). "DARPP-32 May Be Culprit in Schizophrenia Symptoms". Psychiatric News. 37 (18): 24.
- Meister B, Askergren J, Tunevall G, Hemmings HC, Greengard P (September 1991). "Identification of a dopamine- and 3'5'-cyclic adenosine monophosphate-regulated phosphoprotein of 32 kD (DARPP-32) in parathyroid hormone-producing cells of the human parathyroid gland". Journal of Endocrinological Investigation. 14 (8): 655–61. doi:10.1007/bf03347888. PMID 1663529. S2CID 36936723.
- Meister B, Schultzberg M, Hemmings HC, Greengard P, Goldstein M, Hökfelt T (October 1991). "Dopamine- and adenosine-3',5'-monophosphate (cAMP)-regulated phosphoprotein of 32 kDa (DARPP-32) in the adrenal gland: immunohistochemical localization". Journal of the Autonomic Nervous System. 36 (1): 75–84. doi:10.1016/0165-1838(91)90132-M. PMID 1721636.
- Meister B, Arvidsson U, Hemmings HC, Greengard P, Hökfelt T (September 1991). "Dopamine- and adenosine-3':5'-monophosphate (cAMP)-regulated phosphoprotein of Mr 32,000 (DARPP-32) in the retina of cat, monkey and human". Neuroscience Letters. 131 (1): 66–70. doi:10.1016/0304-3940(91)90338-T. PMID 1791981. S2CID 1735579.
- Halpain S, Girault JA, Greengard P (January 1990). "Activation of NMDA receptors induces dephosphorylation of DARPP-32 in rat striatal slices". Nature. 343 (6256): 369–72. Bibcode:1990Natur.343..369H. doi:10.1038/343369a0. PMID 2153935. S2CID 4319592.
- Ouimet CC, Greengard P (February 1990). "Distribution of DARPP-32 in the basal ganglia: an electron microscopic study". Journal of Neurocytology. 19 (1): 39–52. doi:10.1007/BF01188438. PMID 2191086. S2CID 33812522.
- Girault JA, Hemmings HC, Williams KR, Nairn AC, Greengard P (December 1989). "Phosphorylation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, by casein kinase II". The Journal of Biological Chemistry. 264 (36): 21748–59. doi:10.1016/S0021-9258(20)88248-9. PMID 2557337.
- Hemmings HC, Greengard P, Tung HY, Cohen P (1984). "DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1". Nature. 310 (5977): 503–5. Bibcode:1984Natur.310..503H. doi:10.1038/310503a0. PMID 6087160. S2CID 4307053.
- Walaas SI, Greengard P (January 1984). "DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. I. Regional and cellular distribution in the rat brain". The Journal of Neuroscience. 4 (1): 84–98. doi:10.1523/JNEUROSCI.04-01-00084.1984. PMC 6564747. PMID 6319627.
- Brené S, Lindefors N, Ehrlich M, Taubes T, Horiuchi A, Kopp J, Hall H, Sedvall G, Greengard P, Persson H (March 1994). "Expression of mRNAs encoding ARPP-16/19, ARPP-21, and DARPP-32 in human brain tissue". The Journal of Neuroscience. 14 (3 Pt 1): 985–98. doi:10.1523/JNEUROSCI.14-03-00985.1994. PMC 6577526. PMID 8120638.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Kwon YG, Huang HB, Desdouits F, Girault JA, Greengard P, Nairn AC (April 1997). "Characterization of the interaction between DARPP-32 and protein phosphatase 1 (PP-1): DARPP-32 peptides antagonize the interaction of PP-1 with binding proteins". Proceedings of the National Academy of Sciences of the United States of America. 94 (8): 3536–41. Bibcode:1997PNAS...94.3536K. doi:10.1073/pnas.94.8.3536. PMC 20474. PMID 9108011.
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