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

N. J.C. Lamb, J. C. Cavadore, J. C. Labbe, R. A. Maurer, A. Fernandez

Research output: Contribution to journalArticle

74 Scopus citations

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 p34(cdc2) kinase, including the lack of spindle formation and the persistence of a nuclear envelope. In order to examine whether A-kinase inhibition and p34(cdc2) kinase form part of the same or different inductive pathways, PKI and p34(cdc2) 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 p34(cdc2) 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 p34(cdc2) pathway.

Original languageEnglish (US)
Pages (from-to)1523-1533
Number of pages11
JournalEMBO Journal
Volume10
Issue number6
DOIs
StatePublished - Jan 1 1991

Keywords

  • cAMP-dependent protein kinase
  • lamins
  • mitosis
  • nuclear envelope breakdown

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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