Control of Emi2 activity and stability through Mos-mediated recruitment of PP2A.
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.
Wu
Judy Qiju
JQ
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Hansen
David V
DV
Guo
Yanxiang
Y
Wang
Michael Zhuo
MZ
Tang
Wanli
W
Freel
Christopher D
CD
Tung
Jeffrey J
JJ
Jackson
Peter K
PK
Kornbluth
Sally
S
D000595:Amino Acid Sequence; D000818:Animals; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008540:Meiosis; D008969:Molecular Sequence Data; D010063:Ovum / Q000502:physiology*; D010765:Phosphorylase Phosphatase / Q000378:metabolism*; D010766:Phosphorylation; D017231:Proto-Oncogene Proteins c-mos / Q000235:genetics / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
D044783:F-Box Proteins; C498166:FBXO43 protein, Xenopus; D029867:Xenopus Proteins; C495329:Mos protein, Xenopus; D017231:Proto-Oncogene Proteins c-mos; D019893:Ribosomal Protein S6 Kinases; D010765:Phosphorylase Phosphatase