A-kinase anchor proteins as potential regulators of protein kinase A function in oocytes.
In the mammalian oocyte, the cAMP-dependent protein kinase (PKA) has critical functions in the maintenance of meiotic arrest and oocyte maturation. Because PKA is spatially regulated, its localization was examined in developing oocytes. Both regulatory subunits (RI and RII) and the catalytic subunit (C) of PKA were found in oocytes and metaphase II-arrested eggs. In the oocyte, RI and C were predominantly localized in the cortical region, while RII showed a punctate distribution within the cytoplasm. After maturation to metaphase II, RI remained in the cortex and was also localized to the meiotic spindle, while RII was found adjacent to the spindle. C was diffuse within the cytoplasm of the egg but was enriched in the cytoplasm surrounding the metaphase spindle, much like RII. The polarized localization and redistribution of RI, RII, and C suggested that PKA might be tethered by A-kinase anchor proteins (AKAPs), proteins that tether PKA close to its physiological substrates. An AKAP, AKAP140, was identified that was developmentally regulated and phosphorylated in oocytes and eggs. AKAP140 was shown to be a dual-specific AKAP, having the ability to bind both RI and RII. By compartmentalizing PKA, AKAP140 and/or other AKAPs could spatially regulate PKA activity during oocyte development.
Center for Research on Reproduction and Women's Health and Department of Obstetrics & Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Rebecca L
RL
Brown
Teri
T
Ord
Stuart B
SB
Moss
Carmen J
CJ
Williams
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D007163:Immunosorbent Techniques; D008540:Meiosis; D008677:Metaphase; D051379:Mice; D018613:Microscopy, Confocal; D009865:Oocytes / Q000166:cytology / Q000201:enzymology*; D010766:Phosphorylation
D002352:Carrier Proteins; D017868:Cyclic AMP-Dependent Protein Kinases