Characterization and phosphorylation of PDE10A2, a novel alternative splice variant of human phosphodiesterase that hydrolyzes cAMP and cGMP.
We have isolated a novel alternative splice variant of human cAMP- and cGMP-hydrolyzing phosphodiesterase (PDE10A2) from human fetal lung. The N-terminal sequence of human PDE10A2 differed from that of human PDE10A1 reported previously. PDE10A1 and PDE10A2 expressed in COS-7 cells have cGMP K(m) values of 14 and 13 microM, low cAMP K(m) values of 0.28 and 0.22 microM, and high cAMP K(m) values of 0.96 and 1.1 microM, respectively, at high concentrations of cGMP and cAMP. PCR analysis demonstrated that both PDE10A1 and PDE10A2 transcripts are present in various human tissues and that PDE10A2 transcripts are a major form in some human tissues. The unique N-terminus of PDE10A2 has a putative phosphorylation site by cAMP-dependent protein kinase (cAK), but PDE10A1 does not. The recombinant PDE10A2 protein is preferentially phosphorylated by cAK, although the recombinant PDE10A1 protein is not phosphorylated by cAK.
Kotera
J
J
Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd., 2-50, Kawagishi-2-chome, Toda, Saitama, 335-8505, Japan.
Fujishige
K
K
Yuasa
K
K
Omori
K
K
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D006868:Hydrolysis; D008168:Lung / Q000196:embryology / Q000201:enzymology; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
D012333:RNA, Messenger; D011994:Recombinant Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP