XB-ART-36939Proc Natl Acad Sci U S A October 16, 2007; 104 (42): 16564-9.
Before fertilization, vertebrate eggs are arrested in meiosis II by cytostatic factor (CSF), which holds the anaphase-promoting complex (APC) in an inactive state. It was recently reported that Mos, an integral component of CSF, acts in part by promoting the Rsk-mediated phosphorylation of the APC inhibitor Emi2/Erp1. We report here that Rsk phosphorylation of Emi2 promotes its interaction with the protein phosphatase PP2A. Emi2 residues adjacent to the Rsk phosphorylation site were important for PP2A binding. An Emi2 mutant that retained Rsk phosphorylation but lacked PP2A binding could not be modulated by Mos. PP2A bound to Emi2 acted on two distinct clusters of sites phosphorylated by Cdc2, one responsible for modulating its stability during CSF arrest and one that controls binding to the APC. These findings provide a molecular mechanism for Mos action in promoting CSF arrest and also define an unusual mechanism, whereby protein phosphorylation recruits a phosphatase for dephosphorylation of distinct sites phosphorylated by another kinase.
PubMed ID: 17881560
PMC ID: PMC2034268
Article link: Proc Natl Acad Sci U S A
Genes referenced: cdk1 fbxo43 mos ptpa rps6ka1
Morpholinos: fbxo43 MO1 fbxo43 MO2
References [+] :
Bhatt, The protein kinase p90 rsk as an essential mediator of cytostatic factor activity. 1999, Pubmed, Xenbase