Remote hot spots mediate protein substrate recognition for the Cdc25 phosphatase

Jungsan 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
Externally publishedYes

Fingerprint

cdc25 Phosphatases
Cyclin-Dependent Kinases
Xenopus
Phosphoric Monoester Hydrolases
Oocytes
Saccharomyces cerevisiae
Catalytic Domain
Cell Cycle
Proteins
Injections

Keywords

  • Protein-protein interactions

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Remote hot spots mediate protein substrate recognition for the Cdc25 phosphatase. / Sohn, Jungsan; Kristjánsdóttir, K.; Safi, A.; Parker, B.; Kiburz, B.; Rudolph, J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 47, 23.11.2004, p. 16437-16441.

Research output: Contribution to journalArticle

Sohn, Jungsan ; Kristjánsdóttir, K. ; Safi, A. ; Parker, B. ; Kiburz, B. ; Rudolph, J. / Remote hot spots mediate protein substrate recognition for the Cdc25 phosphatase. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 47. pp. 16437-16441.
@article{62f5505fd9de4d629d9377979f3b1e0e,
title = "Remote hot spots mediate protein substrate recognition for the Cdc25 phosphatase",
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 {\AA} 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.",
keywords = "Protein-protein interactions",
author = "Jungsan Sohn and K. Kristj{\'a}nsd{\'o}ttir and A. Safi and B. Parker and B. Kiburz and J. Rudolph",
year = "2004",
month = "11",
day = "23",
doi = "10.1073/pnas.0407663101",
language = "English (US)",
volume = "101",
pages = "16437--16441",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "47",

}

TY - JOUR

T1 - Remote hot spots mediate protein substrate recognition for the Cdc25 phosphatase

AU - Sohn, Jungsan

AU - Kristjánsdóttir, K.

AU - Safi, A.

AU - Parker, B.

AU - Kiburz, B.

AU - Rudolph, J.

PY - 2004/11/23

Y1 - 2004/11/23

N2 - 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.

AB - 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.

KW - Protein-protein interactions

UR - http://www.scopus.com/inward/record.url?scp=9344254385&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9344254385&partnerID=8YFLogxK

U2 - 10.1073/pnas.0407663101

DO - 10.1073/pnas.0407663101

M3 - Article

VL - 101

SP - 16437

EP - 16441

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 47

ER -