The cystic fibrosis transmembrane recruiter the alter ego of CFTR as a multi-kinase anchor

Anil Mehta

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    This review focuses on a newly discovered interaction between protein kinases involved in cellular energetics, a process that may be disturbed in cystic fibrosis for unknown reasons. I propose a new model where kinase-mediated cellular transmission of energy provides mechanistic insight to a latent role of the cystic fibrosis transmembrane conductance regulator (CFTR). I suggest that CFTR acts as a multi-kinase recruiter to the apical epithelial membrane. My group finds that, in the cytosol, two protein kinases involved in cell energy homeostasis, nucleoside diphosphate kinase (NDPK) and AMP-activated kinase (AMPK), bind one another. Preliminary data suggest that both can also bind CFTR (function unclear). The disrupted role of this CFTR-kinase complex as 'membrane transmitter to the cell' is proposed as an alternative paradigm to the conventional ion transport mediated and CFTR/chloride-centric view of cystic fibrosis pathogenesis. Chloride remains important, but instead, chloride-induced control of the phosphohistidine content of one kinase component (NDPK, via a multi-kinase complex that also includes a third kinase, CK2; formerly casein kinase 2). I suggest that this complex provides the necessary near-equilibrium conditions needed for efficient transmission of phosphate energy to proteins controlling cellular energetics. Crucially, a new role for CFTR as a kinase controller is proposed with ionic concentration acting as a signal. The model posits a regulatory control relay for energy sensing involving a cascade of protein kinases bound to CFTR.
    Original languageEnglish
    Pages (from-to)215-221
    Number of pages7
    JournalPflugers Archiv-European Journal of Physiology
    Volume455
    Issue number2
    DOIs
    Publication statusPublished - Nov 2007

    Keywords

    • Cystic Fibrosis
    • Cystic Fibrosis Transmembrane Conductance Regulator
    • Energy Metabolism
    • Homeostasis
    • Humans
    • Protein Binding
    • Protein Kinases

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