Jl. Desseyn et al., Expression of a nonmyristylated variant of the catalytic subunit of protein kinase A during male germ-cell development, P NAS US, 97(12), 2000, pp. 6433-6438
Citations number
33
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
The catalytic subunits of protein kinase A are transcribed in all mouse tis
sues from two distinct genes that code for the C alpha and C beta isoforms.
Alternative promoters exist for the C beta gene that are used in a tissue-
specific fashion and give rise to variants that differ in their amino-termi
nal sequences. We have characterized an alternative promoter that is presen
t in the first intron of the C alpha gene and is transcriptionally active i
n male germ cells. Transcription from this promoter is coincident with the
appearance of pachytene spermatocytes and leads to a C alpha protein (C alp
ha 2) that contains a distinctive 7 amino acid amino-terminus differing fro
m the 14 amino acid amino-terminus of C alpha 1. The C alpha 2 protein does
not contain the myristylation signal present on coil and migrates at a low
er molecular weight on SDS/PACE gels. By Western blotting, we estimate that
most or all of the C alpha protein present in mature sperm is C alpha 2. T
he amino-terminal sequence of C alpha 2 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 cD
NA cloning that human sperm also express a highly related C alpha 2 homolog
. The C alpha 2 subunit forms holoenzymes with either RII alpha or RI alpha
, 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 c
apacitation, the distinctive biochemical properties of the unmyristylated C
alpha 2 may be essential for fertility in the male.