Inhibition of cAMP-dependent protein kinase plays a key role in the induction of mitosis and nuclear envelope breakdown in mammalian cells

Ned J C Lamb, Jean Claude Cavadore, Jean Claude Labbe, Richard Maurer, Anne Fernandez

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Inhibiting cAMP-dependent protein kinase (A-kinase) in mammalian fibroblasts through microinjection of a modified specific inhibitor peptide, PKi(m) or the purified inhibitor protein, PKI, resulted in rapid and pronounced chromatin condensation at all phases of the cell cycle. Together with these changes in chromatin, a marked reorganization of microtubule network occurred, accompanied in G2 cells by extensive alterations in cell shape which have many similarities to the premitotic phenotype previously observed after activation of p34cdc2 kinase, including the lack of spindle formation and the persistence of a nuclear envelope. In order to examine whether A-kinase inhibition and p34cdc2 kinase form part of the same or different inductive pathways, PKI and p34cdc2 kinase were injected together. Co-injection of both components resulted in nuclear envelope disassembly, an event not observed with injection of either component alone. This result implies that p34cdc2 and A-kinase inhibition have complementary and additive effects on the process of nuclear envelope breakdown in living fibroblasts, a conclusion further supported by our observation of a pronounced dephosphorylation of lamins A and C in cells after injection of PKi(m). Taken together, these data suggest that down-regulation of A-kinase is a distinct and essential event in the induction of mammalian cell mitosis which co-operates with the p34cdc2 pathway.

Original languageEnglish (US)
Pages (from-to)1523-1533
Number of pages11
JournalEMBO Journal
Volume10
Issue number6
StatePublished - 1991
Externally publishedYes

Fingerprint

Nuclear Envelope
Cyclic AMP-Dependent Protein Kinases
Mitosis
Phosphotransferases
Cells
Fibroblasts
Injections
Chromatin
Lamin Type A
Cell Shape
Microinjections
Microtubules
Condensation
Cell Cycle
Down-Regulation
Chemical activation
Observation
Phenotype
Peptides
Proteins

Keywords

  • cAMP-dependent protein kinase
  • Lamins
  • Mitosis
  • Nuclear envelope breakdown

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Inhibition of cAMP-dependent protein kinase plays a key role in the induction of mitosis and nuclear envelope breakdown in mammalian cells. / Lamb, Ned J C; Cavadore, Jean Claude; Labbe, Jean Claude; Maurer, Richard; Fernandez, Anne.

In: EMBO Journal, Vol. 10, No. 6, 1991, p. 1523-1533.

Research output: Contribution to journalArticle

Lamb, Ned J C ; Cavadore, Jean Claude ; Labbe, Jean Claude ; Maurer, Richard ; Fernandez, Anne. / Inhibition of cAMP-dependent protein kinase plays a key role in the induction of mitosis and nuclear envelope breakdown in mammalian cells. In: EMBO Journal. 1991 ; Vol. 10, No. 6. pp. 1523-1533.
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