A macromolecular complex of β2 adrenergic receptor, CFTR, and ezrin/radixin/moesin-binding phosphoprotein 50 is regulated by PKA

Anjaparavanda P. Naren, Bryan Cobb, Chunying Li, Koushik Roy, David Nelson, Ghanshyam D. Heda, Jie Liao, Kevin L. Kirk, Eric J. Sorscher, John Hanrahan, John P. Clancy

Research output: Contribution to journalArticle

167 Scopus citations

Abstract

It has been demonstrated previously that both the cystic fibrosis transmembrane conductance regulator (CFTR) and β2 adrenergic receptor (β2AR) can bind ezrin/radixin/moesin-binding phosphoprotein 50 (EBP50, also referred to as NHERF) through their PDZ motifs. Here, we show that β2 is the major adrenergic receptor isoform expressed in airway epithelia and that it colocalizes with CFTR at the apical membrane. β2AR stimulation increases CFTR activity, in airway epithelial cells, that is glybenclamide sensitive. Deletion of the PDZ motif from CFTR uncouples the channel from the receptor both physically and functionally. This uncoupling is specific to the β2AR receptor and does not affect CFTR coupling to other receptors (e.g., adenosine receptor pathway). Biochemical studies demonstrate the existence of a macromolecular complex involving CFTR-EBP50-β2AR through PDZ-based interactions. Assembly of the complex is regulated by PKA-dependent phosphorylation. Deleting the regulatory domain of CFTR abolishes PKA regulation of complex assembly. This report summarizes a macromolecular signaling complex involving CFTR, the implications of which may be relevant to CFTR-dysfunction diseases.

Original languageEnglish (US)
Pages (from-to)342-346
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number1
DOIs
StatePublished - Jan 7 2003

ASJC Scopus subject areas

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