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PMID: 8049524 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Inhibition of cdc2 activation by INH/PP2A.

Molecular biology of the cell ·Vol. 5 ·No. 3 ·1994-03-00 ·Pages 323-38

Lee TH, Turck C, Kirschner MW

Abstract

INH, a type 2A protein phosphatase (PP2A), negatively regulates entry into M phase and the cyclin B-dependent activation of cdc2 in Xenopus extracts. INH appears to be central to the mechanism of the trigger for mitotic initiation, as it prevents the premature activation of cdc2. We first show that INH is a conventional form of PP2A with a B alpha regulatory subunit. We next explore the mechanism by which it inhibits cdc2 activation by examining the effect of purified PP2A on the reaction pathways controlling cdc2 activity. Our results suggest that although PP2A inhibits the switch in tyrosine kinase and tyrosine phosphatase activities accompanying mitosis, this switch is a consequence of the inhibition of some other rate-limiting event. In the preactivation phase, PP2A inhibits the pathway leading to T161 phosphorylation, suggesting that this activity may be one of the rate-limiting events for transition. However, our results also suggest that the accumulation of active cdc2/cyclin complexes during the lag is only one of the events required for triggering entry into mitosis.

MeSH Terms
Animals CDC2 Protein Kinase/metabolism Cyclins/metabolism Enzyme Activation/drug effects Female In Vitro Techniques Kinetics Mitosis/drug effects,physiology Oocytes/cytology,drug effects,metabolism Phosphoprotein Phosphatases/pharmacology Phosphorylation Protein Tyrosine Phosphatases/metabolism Xenopus
Chemicals
Cyclins CDC2 Protein Kinase Phosphoprotein Phosphatases Protein Tyrosine Phosphatases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lee T H
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
Turck C
Kirschner M W
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.5.3.323
Published
1994-03-00
Pages
323-38
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC301040
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.5.3.323 PMC Full Text View journal details
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