Regulation of Cx37 channel and growth-suppressive properties by phosphorylation
AuthorJacobsen, Nicole L.
Pontifex, Tasha K.
Solan, Joell L.
Lampe, Paul D.
Sorgen, Paul L.
Burt, Janis M.
AffiliationUniv Arizona, Dept Physiol
MetadataShow full item record
PublisherCOMPANY OF BIOLOGISTS LTD
CitationRegulation of Cx37 channel and growth-suppressive properties by phosphorylation 2017, 130 (19):3308 Journal of Cell Science
JournalJournal of Cell Science
Rights© 2017. Published by The Company of Biologists Ltd.
Collection InformationThis 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 firstname.lastname@example.org.
AbstractGrowth 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.
Note12 month embargo; Published online: 1 Oct 2017.
VersionFinal published version
SponsorsNational Institutes of Health [HL056732, HL007249, HL131712, GM072631, GM55632, CCSG - CA023074]; American Heart Association [16PRE27500011]
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