PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor-1 and PP1 phosphorylation.
Journal Article (Journal Article)
Loss of cell division cycle 2 (Cdc2, also known as Cdk1) activity after cyclin B degradation is necessary, but not sufficient, for mitotic exit. Proteins phosphorylated by Cdc2 and downstream mitotic kinases must be dephosphorylated. We report here that protein phosphatase-1 (PP1) is the main catalyst of mitotic phosphoprotein dephosphorylation. Suppression of PP1 during early mitosis is maintained through dual inhibition by Cdc2 phosphorylation and the binding of inhibitor-1. Protein kinase A (PKA) phosphorylates inhibitor-1, mediating binding to PP1. As Cdc2 levels drop after cyclin B degradation, auto-dephosphorylation of PP1 at its Cdc2 phosphorylation site (Thr 320) allows partial PP1 activation. This promotes PP1-regulated dephosphorylation at the activating site of inhibitor-1 (Thr 35) followed by dissociation of the inhibitor-1-PP1 complex and then full PP1 activation to promote mitotic exit. Thus, Cdc2 both phosphorylates multiple mitotic substrates and inhibits their PP1-mediated dephosphorylation.
Full Text
Duke Authors
Cited Authors
- Wu, JQ; Guo, JY; Tang, W; Yang, C-S; Freel, CD; Chen, C; Nairn, AC; Kornbluth, S
Published Date
- May 2009
Published In
Volume / Issue
- 11 / 5
Start / End Page
- 644 - 651
PubMed ID
- 19396163
Pubmed Central ID
- PMC2788612
Electronic International Standard Serial Number (EISSN)
- 1476-4679
International Standard Serial Number (ISSN)
- 1465-7392
Digital Object Identifier (DOI)
- 10.1038/ncb1871
Language
- eng