Matches in SemOpenAlex for { <https://semopenalex.org/work/W2003917833> ?p ?o ?g. }
- W2003917833 endingPage "9280" @default.
- W2003917833 startingPage "9268" @default.
- W2003917833 abstract "Protein kinase C (PKC) has been implicated in the control of neurotransmitter release. The AS/AGU rat, which has a nonsense mutation in PKCγ, shows symptoms of parkinsonian syndrome, including dopamine release impairments in the striatum. Here, we found that the AS/AGU rat is PKCγ-knock-out (KO) and that PKCγ-KO mice showed parkinsonian syndrome. However, the PKCγ substrates responsible for the regulated exocytosis of dopamine in vivo have not yet been elucidated. To identify the PKCγ substrates involved in dopamine release, we used PKCγ-KO mice and a phosphoproteome analysis. We found 10 candidate phosphoproteins that had decreased phosphorylation levels in the striatum of PKCγ-KO mice. We focused on Pak-interacting exchange factor-β (βPIX), a Cdc42/Rac1 guanine nucleotide exchange factor, and found that PKCγ directly phosphorylates βPIX at Ser583 and indirectly at Ser340 in cells. Furthermore, we found that PKC phosphorylated βPIX in vivo. Classical PKC inhibitors and βPIX knock-down (KD) significantly suppressed Ca(2+)-evoked dopamine release in PC12 cells. Wild-type βPIX, and not the βPIX mutants Ser340 Ala or Ser583 Ala, fully rescued the decreased dopamine release by βPIX KD. Double KD of Cdc42 and Rac1 decreased dopamine release from PC12 cells. These findings indicate that the phosphorylation of βPIX at Ser340 and Ser583 has pivotal roles in Ca(2+)-evoked dopamine release in the striatum. Therefore, we propose that PKCγ positively modulates dopamine release through β2PIX phosphorylation. The PKCγ-βPIX-Cdc42/Rac1 phosphorylation axis may provide a new therapeutic target for the treatment of parkinsonian syndrome." @default.
- W2003917833 created "2016-06-24" @default.
- W2003917833 creator A5003799324 @default.
- W2003917833 creator A5016734189 @default.
- W2003917833 creator A5019699112 @default.
- W2003917833 creator A5019881008 @default.
- W2003917833 creator A5023392452 @default.
- W2003917833 creator A5035924543 @default.
- W2003917833 creator A5055390938 @default.
- W2003917833 creator A5061115980 @default.
- W2003917833 creator A5070235885 @default.
- W2003917833 creator A5079061263 @default.
- W2003917833 creator A5080606578 @default.
- W2003917833 creator A5083565159 @default.
- W2003917833 creator A5087187446 @default.
- W2003917833 date "2014-07-09" @default.
- W2003917833 modified "2023-10-14" @default.
- W2003917833 title "The Role of Pak-Interacting Exchange Factor- Phosphorylation at Serines 340 and 583 by PKC in Dopamine Release" @default.
- W2003917833 cites W1522048223 @default.
- W2003917833 cites W1576582370 @default.
- W2003917833 cites W1599070069 @default.
- W2003917833 cites W1865055600 @default.
- W2003917833 cites W1938984736 @default.
- W2003917833 cites W1963941913 @default.
- W2003917833 cites W1965542850 @default.
- W2003917833 cites W1969388648 @default.
- W2003917833 cites W1971253332 @default.
- W2003917833 cites W1973193956 @default.
- W2003917833 cites W1978390881 @default.
- W2003917833 cites W1980815431 @default.
- W2003917833 cites W1984711181 @default.
- W2003917833 cites W1985088279 @default.
- W2003917833 cites W1985223881 @default.
- W2003917833 cites W1989777352 @default.
- W2003917833 cites W1993282564 @default.
- W2003917833 cites W2000131429 @default.
- W2003917833 cites W2002000767 @default.
- W2003917833 cites W2003380714 @default.
- W2003917833 cites W2006215870 @default.
- W2003917833 cites W2007101096 @default.
- W2003917833 cites W2011090975 @default.
- W2003917833 cites W2017830053 @default.
- W2003917833 cites W2020954730 @default.
- W2003917833 cites W2021703512 @default.
- W2003917833 cites W2021717885 @default.
- W2003917833 cites W2026198864 @default.
- W2003917833 cites W2026408726 @default.
- W2003917833 cites W2026726511 @default.
- W2003917833 cites W2029952678 @default.
- W2003917833 cites W2031071883 @default.
- W2003917833 cites W2035239343 @default.
- W2003917833 cites W2037844242 @default.
- W2003917833 cites W2041121472 @default.
- W2003917833 cites W2042251760 @default.
- W2003917833 cites W2050259906 @default.
- W2003917833 cites W2051340998 @default.
- W2003917833 cites W2067654943 @default.
- W2003917833 cites W2071661423 @default.
- W2003917833 cites W2077117391 @default.
- W2003917833 cites W2083592023 @default.
- W2003917833 cites W2085082922 @default.
- W2003917833 cites W2086524338 @default.
- W2003917833 cites W2088514516 @default.
- W2003917833 cites W2090748065 @default.
- W2003917833 cites W2092952234 @default.
- W2003917833 cites W2097439505 @default.
- W2003917833 cites W2101527203 @default.
- W2003917833 cites W2109137906 @default.
- W2003917833 cites W2118730668 @default.
- W2003917833 cites W2134927101 @default.
- W2003917833 cites W2139542466 @default.
- W2003917833 cites W2141280199 @default.
- W2003917833 cites W2145573546 @default.
- W2003917833 cites W2148943593 @default.
- W2003917833 cites W2150568244 @default.
- W2003917833 cites W2158052587 @default.
- W2003917833 cites W2160403485 @default.
- W2003917833 cites W2169007182 @default.
- W2003917833 cites W2169549805 @default.
- W2003917833 cites W2274038956 @default.
- W2003917833 doi "https://doi.org/10.1523/jneurosci.4278-13.2014" @default.
- W2003917833 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6608353" @default.
- W2003917833 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25009260" @default.
- W2003917833 hasPublicationYear "2014" @default.
- W2003917833 type Work @default.
- W2003917833 sameAs 2003917833 @default.
- W2003917833 citedByCount "12" @default.
- W2003917833 countsByYear W20039178332015 @default.
- W2003917833 countsByYear W20039178332016 @default.
- W2003917833 countsByYear W20039178332017 @default.
- W2003917833 countsByYear W20039178332018 @default.
- W2003917833 countsByYear W20039178332019 @default.
- W2003917833 countsByYear W20039178332020 @default.
- W2003917833 countsByYear W20039178332022 @default.
- W2003917833 crossrefType "journal-article" @default.
- W2003917833 hasAuthorship W2003917833A5003799324 @default.
- W2003917833 hasAuthorship W2003917833A5016734189 @default.
- W2003917833 hasAuthorship W2003917833A5019699112 @default.