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PDE8A  -  phosphodiesterase 8A

Homo sapiens

 
 
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Disease relevance of PDE8A

  • The C-terminal 545 amino acids of PDE8A (the region shared among all splice variants) were expressed in baculovirus [1].
 

High impact information on PDE8A

  • A 4-fold increase in the sensitivity to LH for testosterone production was detected in Leydig cells isolated from PDE8A knockout mice [2].
  • These observations indicate that PDE8A and at least one other PDE control the same or a complementary pool of cAMP that mediates LH-regulated steroidogenesis [2].
  • By sequence homology in the catalytic domain, PDE9A is almost equidistant from all eight known mammalian PDE families but is most similar to PDE8A (34% amino acid identity) and least like PDE5A (28% amino acid identity) [3].
  • We have isolated cDNAs encoding rat PDE8A and PDE8B from brain and testis, respectively [4].
  • The PDE8A gene is revealed to contain 23 exons, and its exon-intron boundaries have been defined [5].
 

Biological context of PDE8A

 

Anatomical context of PDE8A

  • PDE8A is expressed in a wide variety of tissues as a approximately 4.5 kb mRNA, with highest levels in testis, ovary, small intestine, and colon [1].
  • Overall, these results suggest that pharmacological manipulation of PDE8A, alone or in combination with other PDEs present in Leydig cells, may be exploited to modulate testosterone synthesis and possibly to treat various conditions where the local levels of this androgen need to be altered [2].
  • Northern blot analysis indicated that the mRNA encoding PDE8B is expressed specifically and abundantly in thyroid gland as a approximately 4.2 kb mRNA, in contrast to the wide expression of PDE8A mRNA in various tissues [6].
 

Other interactions of PDE8A

  • PDE8A is most similar to PDE4 (38.5% amino acid identity in the catalytic domain), but is clearly not a member of any of the seven known PDE families [1].
  • The predicted protein sequences of PDE8B showed highest homology (65% identity, 83% similarity) to that of PDE8A [6].
 

Analytical, diagnostic and therapeutic context of PDE8A

References

  1. Isolation and characterization of PDE8A, a novel human cAMP-specific phosphodiesterase. Fisher, D.A., Smith, J.F., Pillar, J.S., St Denis, S.H., Cheng, J.B. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  2. Modulation of Leydig cell function by cyclic nucleotide phosphodiesterase 8A. Vasta, V., Shimizu-Albergine, M., Beavo, J.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. Fisher, D.A., Smith, J.F., Pillar, J.S., St Denis, S.H., Cheng, J.B. J. Biol. Chem. (1998) [Pubmed]
  4. Molecular comparison of rat cyclic nucleotide phosphodiesterase 8 family: unique expression of PDE8B in rat brain. Kobayashi, T., Gamanuma, M., Sasaki, T., Yamashita, Y., Yuasa, K., Kotera, J., Omori, K. Gene (2003) [Pubmed]
  5. Human phosphodiesterase 8A splice variants: cloning, gene organization, and tissue distribution. Wang, P., Wu, P., Egan, R.W., Billah, M.M. Gene (2001) [Pubmed]
  6. Molecular cloning and characterization of human PDE8B, a novel thyroid-specific isozyme of 3',5'-cyclic nucleotide phosphodiesterase. Hayashi, M., Matsushima, K., Ohashi, H., Tsunoda, H., Murase, S., Kawarada, Y., Tanaka, T. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
 
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