PPP1R1B: Difference between revisions
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| ⚫ | '''Protein phosphatase 1, regulatory (inhibitor) subunit 1B (dopamine and cAMP regulated phosphoprotein of 32 kDa, DARPP-32)''', also known as '''PPP1R1B''', is a [[protein]] which in humans is encoded by the ''PPP1R1B'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PPP1R1B protein phosphatase 1, regulatory (inhibitor) subunit 1B (dopamine and cAMP regulated phosphoprotein, DARPP-32)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84152| accessdate = }}</ref><ref name="pmid8120638">{{cite journal | author = Brené S, Lindefors N, Ehrlich M, Taubes T, Horiuchi A, Kopp J, Hall H, Sedvall G, Greengard P, Persson H | title = Expression of mRNAs encoding ARPP-16/19, ARPP-21, and DARPP-32 in human brain tissue | journal = J. Neurosci. | volume = 14 | issue = 3 Pt 1 | pages = 985–98 | year = 1994 | month = March | pmid = 8120638 | doi = | url = http://www.jneurosci.org/cgi/content/abstract/14/3/985 | issn = }}</ref> |
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| ⚫ | '''Protein phosphatase 1, regulatory (inhibitor) subunit 1B (dopamine and cAMP regulated phosphoprotein of 32 kDa, DARPP-32)''', also known as '''PPP1R1B''', is a |
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== Function == |
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| ⚫ | Midbrain dopaminergic neurons play a critical role in multiple brain functions, and abnormal signaling through dopaminergic pathways has been implicated in several major neurologic and psychiatric disorders. One well-studied target for the actions of dopamine is DARPP32. In the densely dopamine- and glutamate-innervated rat caudate-putamen, DARPP32 is expressed in medium-sized spiny neurons (Ouimet and Greengard, 1990) that also express dopamine D1 receptors (Walaas and Greengard, 1984). The function of DARPP32 seems to be regulated by receptor stimulation. Both dopaminergic and glutamatergic (NMDA) receptor stimulation regulate the extent of DARPP32 phosphorylation, but in opposite directions (Halpain et al., 1990). Dopamine D1 receptor stimulation enhances cAMP formation, resulting in the phosphorylation of DARPP32 (Walaas and Greengard, 1984); phosphorylated DARPP32 is a potent protein phosphatase-1 (see MIM 176875) inhibitor (Hemmings et al., 1984). NMDA receptor stimulation elevates intracellular calcium, which leads to activation of calcineurin and dephosphorylation of phospho-DARPP32, thereby reducing the phosphatase-1 inhibitory activity of DARPP32 (Halpain et al., 1990).[supplied by OMIM]<ref name="entrez">{{cite web | title = Entrez Gene: PPP1R1B protein phosphatase 1, regulatory (inhibitor) subunit 1B (dopamine and cAMP regulated phosphoprotein, DARPP-32)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84152| accessdate = }}</ref> |
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== The PPP1R1B gene== |
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This gene is also known as ''DARPP-32'', highlighting its role as a dopamine- and cyclic AMP-regulated phosphoprotein. As such PPP1R1B affects [[dopamine]] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16189209&query_hl=8], [[glutamate]] and [[adenosine]]; and there is some support for a role of the gene in [[schizophrenia]], as well as being involved in the action of multiple drugs including cocaine, amphetamine, nicotine, caffeine, LSD, PCP, ethanol and morphine <ref>Svenningsson P, Nairn AC, Greengard P. DARPP-32 Mediates the Actions of Multiple Drugs of Abuse. AAPS Journal. 2005; 07(02): E353-E360. DOI: 10.1208/aapsj070235 [http://www.aapsj.org/view.asp?art=aapsj070235]</ref>, and in [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16199832&query_hl=8], [[Parkinson's disease]] or EPS (Extra-pyramidal symptoms). |
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This gene is also known as ''DARPP-32'', highlighting its role as a dopamine- and cyclic AMP-regulated phosphoprotein. As such PPP1R1B affects [[dopamine]],<ref name="pmid16189209">{{cite journal | author = Scott L, Forssberg H, Aperia A, Diaz-Heijtz R | title = Locomotor effects of a D1R agonist are DARPP-32 dependent in adult but not weanling mice | journal = Pediatr. Res. | volume = 58 | issue = 4 | pages = 779–83 | year = 2005 | month = October | pmid = 16189209 | doi = 10.1203/01.PDR.0000180553.23507.31 | url = | issn = }}</ref> [[glutamate]] and [[adenosine]]; and there is some support for a role of the gene in [[schizophrenia]], as well as being involved in the action of multiple drugs including cocaine, amphetamine, nicotine, caffeine, LSD, PCP, ethanol and morphine,<ref name="pmid16353915">{{cite journal | author = Svenningsson P, Nairn AC, Greengard P | title = DARPP-32 mediates the actions of multiple drugs of abuse | journal = AAPS J | volume = 7 | issue = 2 | pages = E353–60 | year = 2005 | pmid = 16353915 | doi = 10.1208/aapsj070235 | url = | issn = }}</ref> and in [[Parkinson's disease]] or EPS (Extra-pyramidal symptoms).<ref name="pmid16199832">{{cite journal | author = Clinton SM, Ibrahim HM, Frey KA, Davis KL, Haroutunian V, Meador-Woodruff JH | title = Dopaminergic abnormalities in select thalamic nuclei in schizophrenia: involvement of the intracellular signal integrating proteins calcyon and spinophilin | journal = Am J Psychiatry | volume = 162 | issue = 10 | pages = 1859–71 | year = 2005 | month = October | pmid = 16199832 | doi = 10.1176/appi.ajp.162.10.1859 | url = | issn = }}</ref> |
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A considerable proportion of the psychomotor effects of cannabinoids can be accounted for by a signaling cascade in striatal projection neurons involving PKA-dependent phosphorylation of DARPP-32, achieved via modulation of dopamine D2 and adenosine A2A transmission [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16162925&query_hl=8]. |
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A considerable proportion of the psychomotor effects of cannabinoids can be accounted for by a signaling cascade in striatal projection neurons involving PKA-dependent phosphorylation of DARPP-32, achieved via modulation of dopamine D2 and adenosine A2A transmission.<ref name="pmid16162925">{{cite journal | author = Andersson M, Usiello A, Borgkvist A, Pozzi L, Dominguez C, Fienberg AA, Svenningsson P, Fredholm BB, Borrelli E, Greengard P, Fisone G | title = Cannabinoid action depends on phosphorylation of dopamine- and cAMP-regulated phosphoprotein of 32 kDa at the protein kinase A site in striatal projection neurons | journal = J. Neurosci. | volume = 25 | issue = 37 | pages = 8432–8 | year = 2005 | month = September | pmid = 16162925 | doi = 10.1523/JNEUROSCI.1289-05.2005 | url = | issn = }}</ref> |
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| ⚫ | PPP1R1B has also been associated with improved transfer of information between the [[striatum]] and the [[prefrontal cortex]], suggesting that variants of PPP1R1B can in some circumstances lead to improved and more flexible cognition, while, in the presence of other genetic and environmental factors, it may lead to symptoms of schizophrenia |
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| ⚫ | PPP1R1B has also been associated with improved transfer of information between the [[striatum]] and the [[prefrontal cortex]], suggesting that variants of PPP1R1B can in some circumstances lead to improved and more flexible cognition, while, in the presence of other genetic and environmental factors, it may lead to symptoms of schizophrenia.<ref name="pmid17290303">{{cite journal | author = Meyer-Lindenberg A, Straub RE, Lipska BK, Verchinski BA, Goldberg T, Callicott JH, Egan MF, Huffaker SS, Mattay VS, Kolachana B, Kleinman JE, Weinberger DR | title = Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition | journal = J. Clin. Invest. | volume = 117 | issue = 3 | pages = 672–82 | year = 2007 | month = March | pmid = 17290303 | pmc = 1784004 | doi = 10.1172/JCI30413 | url = | issn = }}</ref> |
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{{PBB_Summary |
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== Discovery == |
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==References== |
==References== |
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Revision as of 20:32, 22 March 2009
Template:PBB Protein phosphatase 1, regulatory (inhibitor) subunit 1B (dopamine and cAMP regulated phosphoprotein of 32 kDa, DARPP-32), also known as PPP1R1B, is a protein which in humans is encoded by the PPP1R1B gene.[1][2]
Function
Midbrain dopaminergic neurons play a critical role in multiple brain functions, and abnormal signaling through dopaminergic pathways has been implicated in several major neurologic and psychiatric disorders. One well-studied target for the actions of dopamine is DARPP32. In the densely dopamine- and glutamate-innervated rat caudate-putamen, DARPP32 is expressed in medium-sized spiny neurons (Ouimet and Greengard, 1990) that also express dopamine D1 receptors (Walaas and Greengard, 1984). The function of DARPP32 seems to be regulated by receptor stimulation. Both dopaminergic and glutamatergic (NMDA) receptor stimulation regulate the extent of DARPP32 phosphorylation, but in opposite directions (Halpain et al., 1990). Dopamine D1 receptor stimulation enhances cAMP formation, resulting in the phosphorylation of DARPP32 (Walaas and Greengard, 1984); phosphorylated DARPP32 is a potent protein phosphatase-1 (see MIM 176875) inhibitor (Hemmings et al., 1984). NMDA receptor stimulation elevates intracellular calcium, which leads to activation of calcineurin and dephosphorylation of phospho-DARPP32, thereby reducing the phosphatase-1 inhibitory activity of DARPP32 (Halpain et al., 1990).[supplied by OMIM][1]
This gene is also known as DARPP-32, highlighting its role as a dopamine- and cyclic AMP-regulated phosphoprotein. As such PPP1R1B affects dopamine,[3] glutamate and adenosine; and there is some support for a role of the gene in schizophrenia, as well as being involved in the action of multiple drugs including cocaine, amphetamine, nicotine, caffeine, LSD, PCP, ethanol and morphine,[4] and in Parkinson's disease or EPS (Extra-pyramidal symptoms).[5]
A considerable proportion of the psychomotor effects of cannabinoids can be accounted for by a signaling cascade in striatal projection neurons involving PKA-dependent phosphorylation of DARPP-32, achieved via modulation of dopamine D2 and adenosine A2A transmission.[6]
PPP1R1B has also been associated with improved transfer of information between the striatum and the prefrontal cortex, suggesting that variants of PPP1R1B can in some circumstances lead to improved and more flexible cognition, while, in the presence of other genetic and environmental factors, it may lead to symptoms of schizophrenia.[7]
Discovery
PPP1R1B was discovered by Paul Greengard and co-workers.[2]
References
- ^ 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 (1994). "Expression of mRNAs encoding ARPP-16/19, ARPP-21, and DARPP-32 in human brain tissue". J. Neurosci. 14 (3 Pt 1): 985–98. PMID 8120638.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Scott L, Forssberg H, Aperia A, Diaz-Heijtz R (2005). "Locomotor effects of a D1R agonist are DARPP-32 dependent in adult but not weanling mice". Pediatr. Res. 58 (4): 779–83. doi:10.1203/01.PDR.0000180553.23507.31. PMID 16189209.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Svenningsson P, Nairn AC, Greengard P (2005). "DARPP-32 mediates the actions of multiple drugs of abuse". AAPS J. 7 (2): E353–60. doi:10.1208/aapsj070235. PMID 16353915.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Clinton SM, Ibrahim HM, Frey KA, Davis KL, Haroutunian V, Meador-Woodruff JH (2005). "Dopaminergic abnormalities in select thalamic nuclei in schizophrenia: involvement of the intracellular signal integrating proteins calcyon and spinophilin". Am J Psychiatry. 162 (10): 1859–71. doi:10.1176/appi.ajp.162.10.1859. PMID 16199832.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Andersson M, Usiello A, Borgkvist A, Pozzi L, Dominguez C, Fienberg AA, Svenningsson P, Fredholm BB, Borrelli E, Greengard P, Fisone G (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". J. Neurosci. 25 (37): 8432–8. doi:10.1523/JNEUROSCI.1289-05.2005. PMID 16162925.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Meyer-Lindenberg A, Straub RE, Lipska BK, Verchinski BA, Goldberg T, Callicott JH, Egan MF, Huffaker SS, Mattay VS, Kolachana B, Kleinman JE, Weinberger DR (2007). "Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition". J. Clin. Invest. 117 (3): 672–82. doi:10.1172/JCI30413. PMC 1784004. PMID 17290303.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)
External links
- An article in 1984 - Full free text available
- Action of Cocaine
- DARPP-32 May Be Culprit In Schizophrenia Symptoms
Further reading
 | This article on a gene on human chromosome 17 is a stub. You can help Wikipedia by expanding it. |