Glucose Activates TORC2-Gad8 Protein via Positive Regulation of the cAMP/cAMP-dependent Protein Kinase A (PKA) Pathway and Negative Regulation of the Pmk1 Protein-Mitogen-activated Protein Kinase Pathway

The mitogen-activated protein kinase-dependent and the cAMP-protein kinase A-dependent signal transduction pathways were studied in cultured mouse oocytes during induced and spontaneous meiotic maturation. The role of the mitogen-activated protein kinase pathway was assessed using PD98059, which specifically inhibits mitogen-activated protein kinase 1 and 2 (that is, MEK1 and MEK2), which activates mitogen-activated protein kinase. The cAMP-dependent protein kinase was studied by treating oocytes with the protein kinase A inhibitor rp-cAMP. Inhibition of the mitogen-activated protein kinase pathway by PD98059 (25 micromol l(-1)) selectively inhibited the stimulatory effect on meiotic maturation by FSH and meiosis-activating sterol (that is, 4,4-dimethyl-5alpha-cholest-8,14, 24-triene-3beta-ol) in the presence of 4 mmol hypoxanthine l(-1), whereas spontaneous maturation in the absence of hypoxanthine was unaffected. This finding indicates that different signal transduction mechanisms are involved in induced and spontaneous maturation. The protein kinase A inhibitor rp-cAMP induced meiotic maturation in the presence of 4 mmol hypoxanthine l(-1), an effect that was additive to the maturation-promoting effect of FSH and meiosis-activating sterol, indicating that induced maturation also uses the cAMP-protein kinase A-dependent signal transduction pathway. In conclusion, induced and spontaneous maturation of mouse oocytes appear to use different signal transduction pathways.

Download Full-text

Taming platelets with cyclic nucleotides11Abbreviations: ABP, actin binding protein; AC, adenylyl cyclase; cAMP, cyclic AMP; cAMP-PK, cAMP-dependent protein kinase; cGMP, cyclic GMP; cGMP-PK, cGMP-dependent protein kinase; DAG, 1,2-diacylglycerol; EDRF, endothelium-derived relaxing factor; GC, guanylyl cyclase; GP, glycoprotein; Hsp27, heat shock protein 27; IP3, inositol 1,4,5- trisphosphate; IRAG, IP3 receptor-associated cGMP-PK substrate; MAPK, mitogen-activated protein kinase; MAPKAPK-2, MAPK-activated protein kinase-2; MARCKS, myristoylated alanine-rich C kinase substrate; MLC, myosin light chain; MLCK, myosin light chain kinase; PDE, phosphodiesterase; PG-E1, prostaglandin E1; PG-I2, prostacyclin; PIP2, phosphatidylinositol 4,5-bisphosphate; PKC, protein kinase C; PLC, phospholipase C; TxA2, thromboxane A2, and VASP, vasodilator-stimulated phosphoprotein.

Biochemical Pharmacology ◽

10.1016/s0006-2952(01)00760-2 ◽

2001 ◽

Vol 62 (9) ◽

pp. 1153-1161 ◽

Cited By ~ 230

Author(s):

Ulrike R. Schwarz ◽

Ulrich Walter ◽

Martin Eigenthaler

Keyword(s):

Protein Kinase ◽

Light Chain ◽

Myosin Light Chain ◽

Mitogen Activated Protein Kinase ◽

Actin Binding ◽

Ip3 Receptor ◽

Dependent Protein Kinase ◽

Kinase Substrate ◽

Mitogen Activated Protein ◽

Dependent Protein

Download Full-text

Protein kinase A acts at multiple points to inhibit Xenopus oocyte maturation

Molecular and Cellular Biology ◽

10.1128/mcb.14.7.4419-4426.1994 ◽

1994 ◽

Vol 14 (7) ◽

pp. 4419-4426

Author(s):

W Matten ◽

I Daar ◽

G F Vande Woude

Keyword(s):

Protein Kinase ◽

Xenopus Oocytes ◽

Negative Regulator ◽

Mitogen Activated Protein Kinase ◽

Mobility Shift ◽

Dependent Protein Kinase ◽

Multiple Points ◽

Mitogen Activated Protein ◽

Dependent Protein ◽

Phosphatase Activation

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.

Download Full-text