IDENTIFICATION AND TISSUE-SPECIFIC EXPRESSION OF PDE7 PHOSPHODIESTERASE SPLICE VARIANTS

Type 7 cyclic nucleotide phosphodiesterases (PDE7s) are a newly descri bed family of enzymes having high affinity and specificity for cAMP. H owever, little is known about their structure, function, or regulation , We have isolated a mouse skeletal muscle cDNA representing a new alt ernative splice variant (PDE7A2) of the PDE7 gene, The ORF encodes a 4 56-amino acid protein having a predicted molecular weight of 52.4 kDa, The 5' end of the mouse PDE7A2 is divergent from the 5' end of the hu man PDE7A1 sequence and is more hydrophobic. A comparison of the 5' en ds of the two cDNA clones with human genomic sequence indicates that t hey represent alternate splice products rather than species variation, RNase protection analysis of several mouse tissues indicates that PDE 7 is expressed widely with highest levels in skeletal muscle, HPLC fra ctionation and Western blot analysis of two human lymphocyte T-cell li nes shows that an unknown PDE activity described by Ichimura and Kase [Ichimura, M. & Kase, H. (1993) Biochem, Biophys. Res, Commun. 193, 98 5-990] is most likely to be PDE7A1, A single immunoreactive band of ap proximate to 55 kDa, which comigrates with PDE7A1, is seen in fraction s of the HPLC profile containing this activity suggesting that the ori ginal human PDE7A1 clone contains a full-length ORF, and is not trunca ted at the 5' end as was originally postulated, In a human lymphocyte B-cell line and also in mouse skeletal muscle, a large amount of PDE7 mRNA but little PDE7 protein or activity is expressed suggesting that the translation or stability of PDE7 protein may be highly regulated i n these tissues.