Control of G2/M transition in Xenopus by a member of the p21-activated kinase (PAK) family:: A link between protein kinase a and PAK signaling pathways?

X-PAKs are involved in negative control of the process of oocyte maturation in Xenopus (1), In the present study, we define more precisely the events targetted by the kinase in the inhibition of the G(2)/M transition. We show that microinjection of recombinant X-PAK1-Cter active kinase into progesterone-treated oocytes prevents c-Mos accumulation and activation of both MAPK and maturation-promoting factor (MPF), In conditions permissive for MAPK activation, MPF activation still fails. We demonstrate that a constitutive truncated version of X-PAK1 (X-PAK1-Cter) does not prevent the association of cyclin B with p34(cdc2) but rather prevents the activation of the inactive complexes present in the oocyte. Proteins participating in the MPF amplification loop, including the Cdc25-activating Polo-like kinase are all blocked. Indeed, using active MPF, the amplification loop is not turned on in the presence of X-PAK1. Our results indicate that X-PAK and protein kinase A targets in the control of oocyte maturation are similar and furthermore that this negative regulation is not restricted to meiosis, because we demonstrate that G(2)/M progression is also prevented in Xenopus cycling extracts in the presence of active X-PAK1.