Remote hot spots mediate protein substrate recognition for the Cdc25 phosphatase

J. Sohn, K. Kristjánsdóttir, A. Safi, B. Parker, B. Kiburz, J. Rudolph

Research output: Contribution to journalArticle

Abstract

Cdc25B is a phosphatase that catalyzes the dephosphorylation and activation of the cyclin-dependent kinases, thus driving cell cycle progression. We have identified two residues, R488 and Y497, located >20 Å from the active site, that mediate protein substrate recognition without affecting activity toward small-molecule substrates. Injection of Cdc25B wild-type but not the R488L or Y497A variants induces germinal vesicle breakdown and cyclin-dependent kinase activation in Xenopus oocytes. The conditional knockout of the cdc25 homolog (mih1) in Saccharomyces cerevisiae can be complemented by the wild type but not by the hot spot variants, indicating that protein substrate recognition by the Cdc25 phosphatases is an essential and evolutionarily conserved feature.

Original languageEnglish (US)
Pages (from-to)16437-16441
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number47
DOIs
StatePublished - Nov 23 2004

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Keywords

  • Protein-protein interactions

ASJC Scopus subject areas

  • General

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