Protein kinase A acts at multiple points to inhibit Xenopus oocyte maturation.
In Xenopus oocytes, initiation of maturation is dependent on reduction of cyclic AMP-dependent protein kinase (PKA) activity and the synthesis of the mos proto-oncogene product. Mos is required during meiosis I for the activation of both maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK). Here we show that injection of the catalytic subunit of PKA (PKAc) prevented progesterone-induced synthesis of endogenous Mos as well as downstream MPF and MAPK activation. However, PKAc did not prevent injected soluble Mos product from activating MAPK. While MAPK is activated during Mos-PKAc coinjection, attendant MPF activation is blocked. Additionally, PKAc caused a potent block in the electrophoretic mobility shift of cdc25 that is associated with phosphatase activation. This inhibition of cdc25 activity was not reversed by progesterone, Mos, or MPF. We conclude that PKAc acts as a negative regulator at several points in meiotic maturation by preventing both Mos translation and MPF activation.
Matten
W
W
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702.
Daar
I
I
Vande Woude
G F
GF
D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D016200:Maturation-Promoting Factor / Q000378:metabolism; D008540:Meiosis; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000302:isolation & purification / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism; D017231:Proto-Oncogene Proteins c-mos / Q000096:biosynthesis*; D019908:Proto-Oncogene Proteins c-raf; D011519:Proto-Oncogenes; D014982:Xenopus laevis; D020687:cdc25 Phosphatases
D011518:Proto-Oncogene Proteins; D011374:Progesterone; D017346:Protein Serine-Threonine Kinases; D017231:Proto-Oncogene Proteins c-mos; D019908:Proto-Oncogene Proteins c-raf; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016200:Maturation-Promoting Factor; D010749:Phosphoprotein Phosphatases; D020687:cdc25 Phosphatases