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Ppp1r14d  -  protein phosphatase 1, regulatory...

Mus musculus

Synonyms: 2010107K19Rik, GBPI-1, Gastrointestinal and brain-specific PP1-inhibitory protein 1, Gbpi, Ppp1r14, ...
 
 

 

  • The shorter mRNA that encodes mouse GBPI-1 of 146 amino acid polypeptide, is expressed in brain, stomach, small intestine, colon and kidney, whereas a longer GBPI-2 of 175 amino acid polypeptide splice variant mRNA is found in testis where shorter isoform of GBPI-1 is absent [1] [2].
  • Recombinant GBPI-1-fusion protein inhibits PP1 activity with IC50=3 nM after phosphorylation by PKC [1].
  • When PKC-phosphorylated GBPI-1 is further phosphorylated by PKA, it no longer inhibits PP1. Thus, GBPI-1 is well positioned to integrate PKC and PKA modulation of PP1 to regulate deferential protein phosphorylation patterns in brain and gut [3].
  • GBPI contains a consensus PP1-binding motif at residues 21–25 (KKVHW) and consensus sites for phosphorylation by several kinases, including PKC, PKA and casein kinase II [3] [4].
  • Each of the mutations in amino acids located in potential PP1-binding sequences,K21E+K22E and W25A, decrease the ability of GBPI-1 to inhibit PP1. Mutations in the potential PKC phosphoacceptor site T58E also dramatically decrease the ability of GBPI-1 to inhibit PP1 [3].

References

  1. GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA. Liu, Q.R., Zhang, P.W., Lin, Z., Li, Q.F., Woods, A.S., Troncoso, J., Uhl, G.R. Biochem. J. (2004) [Pubmed]
  2. Families of protein phosphatase 1 modulators activated by protein kinases a and C: focus on brain. Liu, Q.R., Gong, J.P., Uhl, G.R. Prog. Nucleic. Acid. Res. Mol. Biol. (2005) [Pubmed]
  3. GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA. Liu, Q.R., Zhang, P.W., Lin, Z., Li, Q.F., Woods, A.S., Troncoso, J., Uhl, G.R. Biochem. J. (2004) [Pubmed]
  4. Regulation of cellular protein phosphatase-1 (PP1) by phosphorylation of the CPI-17 family, C-kinase-activated PP1 inhibitors. Eto, M. J. Biol. Chem. (2009) [Pubmed]
 
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