Transgenic expression of protein phosphatase 2A regulatory subunit B56γ disrupts distal lung differentiation

Allen D. Everett, Craig Kamibayashi, David L. Brautigan

Research output: Contribution to journalArticlepeer-review

Abstract

The distal epithelium of the developing lung exhibits high-level expression of protein phosphatase 2A (PP2A), a vital signaling enzyme. Here we report the discovery that in the lung, the PP2A regulatory subunit B56γ is expressed in a discrete developmental period, with the highest protein levels at embryonic day (e) 17, but no detectable protein in the newborn or adult. By in situ hybridization, B56γ was highly expressed in the distal epithelium of newly forming airways and in mesenchymal cells. In contrast, expression of B56γ was quite low in the bronchial epithelium and vascular smooth muscle. Transgenic expression of B56γ using the lung-specific promoter for surfactant protein C (SP-C) resulted in neonatal death. Examination of lungs from SP-C-B56γ transgenic e18 fetuses revealed proximal airways and normal blood vessels, but the tissue was densely populated with epithelial-type cells and was devoid of normal peripheral lung structure. A component of the Wnt signaling pathway, β-catenin, was developmentally regulated in the normal lung and was absent in lung tissue from B-56γ transgenic fetuses. We propose that B56γ is expressed at a particular stage of lung development to modulate PP2A action on the Wnt/β-catenin signaling pathway during lung airway morphogenesis.

Original languageEnglish (US)
Pages (from-to)L1266-L1271
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume282
Issue number6 26-6
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Lung development
  • PP2A
  • Wnt
  • β-catenin

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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