PBX1 nuclear export is regulated independently of PBX-MEINOX interaction by PKA phosphorylation of the PBC-B domain

Charlotte Kilstrup-Nielsen, Massimo Alessio, Vincenzo Zappavigna

Research output: Contribution to journalArticle

Abstract

The regulation of PBC protein function through subcellular distribution is a crucial evolutionarily conserved mechanism for appendage patterning. We investigated the processes controlling PBX1 nuclear export. Here we show that in the absence of MEINOX proteins nuclear export is not a default pathway for PBX1 subcellular localization. In different cell backgrounds, PBX1 can be imported or exported from the nucleus independently of its capacity to interact with MEINOX proteins. The cell context-specific balance between nuclear export and import of PBX1 is controlled by the PBC-B domain, which contains several conserved serine residues corresponding to phosphorylation sites for Ser/Thr kinases. PBX1 subcellular localization correlates with the phosphorylation state of these residues whose dephosphorylation induces nuclear export. Protein kinase A (PKA) specifically phosphorylates PBX1 at these serines, and stimulation of endogenous PKA activity in vivo blocks PBX1 nuclear export in distal limb mesenchymal cells. Our results reveal a novel mechanism for the control of PBX1 nuclear export in addition to the absence of MEINOX protein, which involves the inhibition of PKA-mediated phosphorylation at specific sites within the PBC-B domain.

Original languageEnglish
Pages (from-to)89-99
Number of pages11
JournalEMBO Journal
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 2 2003

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Private telephone exchanges
Phosphorylation
Cell Nucleus Active Transport
Cyclic AMP-Dependent Protein Kinases
Serine
Proteins
Nuclear Proteins
Phosphotransferases
Extremities

Keywords

  • Homeodomain
  • Limb patterning
  • Nuclear export
  • Nuclear import
  • Post-translational regulation

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

PBX1 nuclear export is regulated independently of PBX-MEINOX interaction by PKA phosphorylation of the PBC-B domain. / Kilstrup-Nielsen, Charlotte; Alessio, Massimo; Zappavigna, Vincenzo.

In: EMBO Journal, Vol. 22, No. 1, 02.01.2003, p. 89-99.

Research output: Contribution to journalArticle

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