Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins

K Galaktionov1, D Beach

  • 1Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.

Cell
|December 20, 1991
PubMed

Insights

Two new human CDC25 genes, cdc25A and cdc25B, were identified. They activate tyrosine phosphatase and are regulated by B-type cyclins, crucial for cell cycle control.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The CDC25 gene product is a key regulator of cell cycle progression.
  • Tyrosine phosphorylation plays a critical role in cell cycle control.

Purpose of the Study:

  • To identify and characterize novel human CDC25 genes.
  • To investigate the regulatory mechanisms of CDC25 tyrosine phosphatase activity.

Main Methods:

  • Gene isolation and functional rescue of fission yeast mutants.
  • Antibody microinjection into HeLa cells to study mitotic arrest.
  • In vitro assays to measure tyrosine phosphatase activity and protein interactions.

Main Results:

  • Two novel human CDC25 genes, cdc25A and cdc25B, were isolated and functionally characterized.
  • cdc25A and cdc25B exhibit tyrosine phosphatase activity, stimulated by B-type cyclins (B1, B2) but not other cyclin types.
  • Association between cdc25A, cyclin B1, and cdc2 was observed in HeLa cells.
  • A conserved motif for cyclin interaction was identified in tyrosine phosphatases but absent in cdc25.

Conclusions:

  • B-type cyclins are multifunctional, regulating both cdc2 kinase activity and cdc25 tyrosine phosphatase activation.
  • cdc25A and cdc25B are key components in the cell cycle control pathway, activated by B-type cyclins.
  • Intermolecular interaction with cyclin B likely provides an activating domain to cdc25 phosphatases.

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