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PMID: 9482921 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identification of a substrate-targeting domain in cyclin E necessary for phosphorylation of the retinoblastoma protein.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 5 ·1998-03-03 ·Pages 2535-40

Kelly BL, Wolfe KG, Roberts JM

Abstract

Considerable advances have been made in characterizing the cyclins and cyclin-dependent kinases (CDKs) that are necessary for progression through the cell cycle, but there has been relatively lesser success in identifying the specific biochemical pathways and cell cycle events that are directly under CDK control. To identify physiologically significant CDK substrates we generated mutations in cyclin E that altered the ability of the cyclin to direct the cyclin-CDK holoenzyme to specific in vivo substrates. We show that one of these mutations defines a domain in cyclin E necessary for phosphorylation of the retinoblastoma protein (Rb). These observations confirm the idea that cyclins contribute to substrate recognition by cyclin-CDK complexes, demonstrate the utility of targeting mutants in the identification of essential cyclin-CDK substrates, and put cyclin E squarely into the family of proteins designed to regulate Rb.

MeSH Terms
3T3 Cells Alanine Amino Acid Sequence Animals Binding Sites Cloning, Molecular Cyclin E/chemistry,metabolism Humans Kinetics Mice Mutagenesis, Site-Directed Phenotype Phosphorylation Point Mutation Recombinant Proteins/chemistry,metabolism Retinoblastoma Protein/chemistry,metabolism Substrate Specificity Transfection
Chemicals
Cyclin E Recombinant Proteins Retinoblastoma Protein Alanine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kelly B L
Fred Hutchinson Cancer Research Center, Division of Basic Sciences, 1124 Columbia Street, Seattle, WA 98104, USA.
Wolfe K G
Roberts J M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.5.2535
Published
1998-03-03
Pages
2535-40
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC19404
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.95.5.2535 PMC Full Text View journal details
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