Figure one: note the photos of the Xenopus oocyte on the bottom. The dark animal pole is where the pigment granules and nucleus are located, and the white vegetal pole is at the bottom -where yolk is stored. The white spot appears at meiosis I (MI).
It is believed that progesterone (PG) binds to a seven-transmembrane domain receptor located in the plasma membrane (this of course is very unusual; most steroids enter the cytoplasm to bind to a receptor that then goes into the nucleus to alter gene activity; see Science 300:594, 2003). Then Protein kinase A (cAMP dept protein kinase; PKA) is somehow inhibited by the bound progesterone receptor (the progesterone receptor would inhibit Gs or stimulate Gi).
Without progesterone, PKA inhibits both Mos and Polo-Like Kinase Kinase 1 (PLKK1). With progesterone, PKA activity drops and PLKK1 and Mos are active.
In one subsequent path, Mos activates Map kinase kinase (or MEK; this kinase can be inhibited by the drug U0126), which activates Map kinase (MAPK) which can feedback and activate Mos, and Map kinase stimulates RSK (an S6 kinase). Rsk then inhibits myt 1 (a dual specificity kinase). Since myt inhibits Maturation Promoting Factor (also called M phase or meiosis promoting factor; MPF; more specifically), inhibition of myt leads to MPF activation. Myt inhibits formation of the MPF complex of cdc2 kinase and cyclin.
There is a second path involved here too: activated PLKK1 activates "Polo-Like Kinase from Xenopus" (PLX), which turns on CDC25. The latter is a phosphatase that removes inhibitory phosphorylation from cdc2 (a subunit of MPF). This also activates MPF.
Note that the activity of MPF is graphed in the lower part of the figure. It increases first to induce the white spot appearance (the white spot is produced when MPF causes the nucleus moves up near the surface to push away pigment granules). After this first peak of MPF, there is a second peak of MPF about 1.5 hrs after white spot appearance- this produces the Meiosis II stage (MII).
Note that MPF can induce two positive feedback systems by stimulating both cdc25 and Mos; but MPF can also stimulate its own destruction (through stimulation of APC activity; APC destroys cyclin of MPF, turning off MPF). Thus, the second rise in MPF is due to a decrease in MPF (APC destruction of the initial peak of MPF) and then inhibition of APC by both CSF and Bub 1.
To be fertilizable, the cell must reach this second Meiosis II stage (MII). There are many changes (such as calcium store development, development of connections between cortical calcium stores and the plasma membranes, etc) that take place during oocyte maturation to the egg that leads to successful fertilization. In addition, note that rise in Cytostatic Factor (CSF) activity at MI. CSF keeps MPF activity high (because it inhibits the degradative system called APC) and the cell arrests in meiosis II. Normally, APC would destroy MPF activity and this allows meiosis to finish.
Since MPF activity has to decrease to allow anaphase to begin, if MPF is maintained high by CSF, the cell arrests in metaphase II of meiosis (MII).
Only when the cell is fertilized, and the calcium level increases, is CSF destroyed. MPF activity then decreases and the zygote is allowed to finish meiosis.
How does insulin work? It is believed that it enters at the level of MEK.
Fig. 2
