Progesterone but not ras requires MPF for in vivo activation of MAPK and S6 KII: MAPK is an essential conexion point of both signaling pathways

Abstract

Induction of mitosis in Xenopus laevis oocytes by hormones and the oncogenic ras-p21 protein has been shown to correlate with a cascade of phosphorylations of the Ser/Thr family of kinases. However, the exact hierarchy of enzymes and their mutual interdependency has not been fully elucidated yet. We have used the Xenopus laevis system to investigate the mechanism of activation of the Ser/Thr kinases cascade and their relationship. Comparison between progesterone-induced germinal vesicle breakdown (GVBD), a hallmark of mitosis in oocytes, to that triggered by ras-p21, revealed the existence of at least two independent mechanisms to activate the MAP kinase enzyme in vivo. While progesterone function is dependent of cdc2 protein kinase activity, ras-p21 is independent of this enzyme. However, both progesterone and ras-p21 converge at the MAP kinase level, and depletion of MAP kinase activity inhibits the GVBD and S6 kinase II activation induced by both progesterone and ras-p21. These results provides further evidence that MAP kinase is a critical step for regulation of the cell cycle in oocytes and a critical point where ras and progesterone signaling converge.

Activation of Intracellular Kinases inXenopusOocytes by p21rasand Phospholipases: a Comparative Study

“…MAPK is activated by progesterone and p21 ras , and this activation is necessary for oocyte maturation (8,20). These results are in agreement with previous observations indicating that oocyte maturation requires MPF in progesterone-but not ras-induced GVBD (34).…”

“…Therefore, inducers that activate MAP K should also activate S6 KII. Progesterone and oncogenic p21 ras activate S6 KII through activation of MAP K (8). We show that PLD, which activates p42 MAPK , also activates S6 KII.…”

“…In particular, 2-AP blocks ras-induced activation of p44 ERK1 in PC12 cells (42) and in X. laevis oocytes (8). Therefore, we studied the effects of 2-AP treatment on the intracellular signals generated by progesterone and PLs and compared them with those induced by …”

“…After the stimulation with hormones, MAP kinase (MAP K) is activated during the M-phase transition under the control of MPF, and it may constitute part of the kinase cascade downstream of MPF (13,15,31). However, while p21 ras induces MAP K activation without MPF activation (8,34), MAP K activation still seems to be necessary for GVBD induced by progesterone and p21 ras (8,20). Moreover, p42 MAPK phosphorylates and activates S6 kinase II (KII) (48), the Xenopus homolog of mammalian pp90 rsk (11).…”

Xenopus H-RasV12 promotes entry into meiotic M phase and cdc2 activation independently of Mos and p42MAPK

“…Microinjection of the oncogenic human HRas in prophase oocyte induces maturation, with a slow GVBD time-course compared to progesterone (Birchmeier et al, 1985). Despite some contradiction in the literature, it is generally proposed that human oncogenic Ras-induced cdc2 activation would implicate the Raf/MEK/p42 MAPK pathway (Barrett et al, 1990;Carnero et al, 1994;Daar et al, 1991;Fukuda et al, 1994;Nebreda et al, 1993b;Pomerance et al, 1996).…”