Regulation of the cdc25 protein during the cell cycle in Xenopus extracts

Cell. 1992 Jul 10;70(1):139-51. doi: 10.1016/0092-8674(92)90540-s.

Abstract

The cdc25 protein is a highly specific tyrosine phosphatase that triggers mitosis by dephosphorylating the cdc2 protein kinase. Using Xenopus extracts, we have found that the cdc25 protein is active at a low level throughout interphase. Near the onset of mitosis, the cdc25 protein undergoes a marked elevation in phosphatase activity that coincides with an extensive phosphorylation of the protein in its N-terminal region. In vitro dephosphorylation of this hyperphosphorylated form of cdc25 reduces its phosphatase activity back to the interphase level. Moreover, treatment of interphase Xenopus extracts with okadaic acid, a phosphatase inhibitor that accelerates the entry into mitosis, elicits both the premature hyperphosphorylation of cdc25 and the stimulation of its cdc2-specific tyrosine phosphatase activity. These experiments demonstrate the existence of a cdc25 regulatory system consisting of both a stimulatory kinase that phosphorylates a putative regulatory domain of the cdc25 protein and an inhibitory serine/threonine phosphatase that counteracts this kinase activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Enzyme Activation / drug effects
  • Enzyme Repression / drug effects
  • Ethers, Cyclic / pharmacology
  • Mitosis*
  • Molecular Sequence Data
  • Okadaic Acid
  • Open Reading Frames
  • Ovum / enzymology
  • Phosphorylation
  • Protein Biosynthesis*
  • Protein Tyrosine Phosphatases / metabolism*
  • Proteins / antagonists & inhibitors
  • Xenopus / physiology
  • cdc25 Phosphatases

Substances

  • Ethers, Cyclic
  • Proteins
  • Okadaic Acid
  • Protein Tyrosine Phosphatases
  • cdc25 Phosphatases

Associated data

  • GENBANK/L05499
  • GENBANK/M87278
  • GENBANK/M94262
  • GENBANK/M94263
  • GENBANK/M94264
  • GENBANK/S72766
  • GENBANK/S72767
  • GENBANK/S72768
  • GENBANK/S72769
  • GENBANK/S72771