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    Regulation of Cx37 channel and growth-suppressive properties by phosphorylation

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    Author
    Jacobsen, Nicole L.
    Pontifex, Tasha K.
    Li, Hanjun
    Solan, Joell L.
    Lampe, Paul D.
    Sorgen, Paul L.
    Burt, Janis M. cc
    Affiliation
    Univ Arizona, Dept Physiol
    Issue Date
    2017-10-01
    Keywords
    Gap junction
    Connexin
    Cell cycle
    Apoptosis
    Gating
    Phosphorylation
    
    Metadata
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    Publisher
    COMPANY OF BIOLOGISTS LTD
    Citation
    Regulation of Cx37 channel and growth-suppressive properties by phosphorylation 2017, 130 (19):3308 Journal of Cell Science
    Journal
    Journal of Cell Science
    Rights
    © 2017 The Author(s). Published by The Company of Biologists Ltd.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    Growth suppression mediated by connexin 37 (Cx37; also known as GJA4) requires interaction between its C-terminus and functional pore-forming domain. Using rat insulinoma cells, we show that Cx37 induces cell death and cell cycle arrest, and slowed cell cycling. Whether differential phosphorylation might regulate intramolecular interactions, and consequently the growth-suppressive phenotype, is unknown. Protein kinase C inhibition increased the open state probability of low-conductance gap junction channels (GJChs) and reduced GJCh closed state probability. Substituting alanine at serine residues 275, 302 and 328 eliminated Cx37-induced cell death, supported proliferation and reduced the GJCh closed state probability. With additional alanine for serine substitutions at residues 285, 319, 321 and 325, Cx37-induced cell death was eliminated and the growth arrest period prolonged, and GJCh closed state probability was restored. With aspartate substitution at these seven sites, apoptosis was induced and the open state probability of large conductance GJChs (and hemichannels) was increased. These data suggest that differential phosphorylation of the C-terminus regulates channel conformation and, thereby, cell cycle progression and cell survival.
    Note
    12 month embargo; Published online: 1 Oct 2017.
    ISSN
    0021-9533
    1477-9137
    PubMed ID
    28818996
    DOI
    10.1242/jcs.202572
    Version
    Final published version
    Sponsors
    National Institutes of Health [HL056732, HL007249, HL131712, GM072631, GM55632, CCSG - CA023074]; American Heart Association [16PRE27500011]
    Additional Links
    http://jcs.biologists.org/lookup/doi/10.1242/jcs.202572
    ae974a485f413a2113503eed53cd6c53
    10.1242/jcs.202572
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