Expression of a nonmyristylated variant of the catalytic subunit of protein kinase A during male germ-cell development

The catalytic subunits of protein kinase A are transcribed in all mouse tissues from two distinct genes that code for the Cα and Cβ isoforms. Alternative promoters exist for the Cβ gene that are used in a tissue-specific fashion and give rise to variants that differ in their amino-terminal sequences. We have characterized an alternative promoter that is present in the first intron of the Cα gene and is transcriptionally active in male germ cells. Transcription from this promoter is coincident with the appearance of pachytene spermatocytes and leads to a Cα protein (Cα2) that contains a distinctive 7 amino acid amino-terminus differing from the 14 amino acid amino-terminus of Cα1. The Cα2 protein does not contain the myristylation signal present on Cα1 and migrates at a lower molecular weight on SDS/PAGE gels. By Western blotting, we estimate that most or all of the Cα protein present in mature sperm is Cα2. The amino-terminal sequence of Cα2 is similar to that of ovine sperm C as previously reported [San Agustin, J. T., Leszyk, J. D., Nuwaysir, L. M. & Witman, G. B. (1998) J. Biol. Chem. 273, 24874–24883], and we show by cDNA cloning that human sperm also express a highly related Cα2 homolog. The Cα2 subunit forms holoenzymes with either RIIα or RIα, and both activate at the same concentration of cyclic nucleotide. Because protein kinase A is thought to play a pivotal role in sperm motility and capacitation, the distinctive biochemical properties of the unmyristylated Cα2 may be essential for fertility in the male.