Volume 272, Number 26, Issue of June 27, 1997 pp. 16152-16157
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Alternative Splicing of the High Affinity cAMP-Specific Phosphodiesterase (PDE7A) mRNA in Human Skeletal Muscle and Heart

(Received for publication, August 30, 1996, and in revised form, March 24, 1997)

From the Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx,  New York 10461

To further our understanding of the structure and function of phosphodiesterases of the newly identified family of high affinity cAMP-specific phosphodiesterases (PDE7), we identified and characterized the isozyme expressed in human skeletal muscle and the protein product of the previously isolated isozyme HCP1 (designated HSPDE7A1). We report the isolation of a cDNA encoding the full-length skeletal muscle isoform of human PDE7A (HSPDE7A2). The DNA sequence of this skeletal muscle cDNA indicates that PDE7A2 is a novel 5 splice variant of PDE7A encoding an isoform with a novel, hydrophobic N terminus. The 456-amino acid PDE7A2 protein is detected on Western blots as a band with an apparent mobility of 50 kDa. PDE7A2 is a high affinity cAMP-specific PDE (K_m = 0.1 µM), which is localized to particulate cellular fractions. The PDE7A1 (HCP1) isozyme is detected on Western blots as a band with an apparent mobility of 57 kDa, demonstrating that the previously isolated HCP1 cDNA encodes the full-length PDE7A1 protein. The even distribution of PDE7A mRNA among fetal tissues and the relative abundance of its two mRNAs strongly suggest that the expression of PDE7A is regulated throughout development.

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