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dc.contributor.authorJacobsen, Nicole L.
dc.contributor.authorPontifex, Tasha K.
dc.contributor.authorLi, Hanjun
dc.contributor.authorSolan, Joell L.
dc.contributor.authorLampe, Paul D.
dc.contributor.authorSorgen, Paul L.
dc.contributor.authorBurt, Janis M.
dc.date.accessioned2017-11-06T22:25:18Z
dc.date.available2017-11-06T22:25:18Z
dc.date.issued2017-10-01
dc.identifier.citationRegulation of Cx37 channel and growth-suppressive properties by phosphorylation 2017, 130 (19):3308 Journal of Cell Scienceen
dc.identifier.issn0021-9533
dc.identifier.issn1477-9137
dc.identifier.pmid28818996
dc.identifier.doi10.1242/jcs.202572
dc.identifier.urihttp://hdl.handle.net/10150/625983
dc.description.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.
dc.description.sponsorshipNational Institutes of Health [HL056732, HL007249, HL131712, GM072631, GM55632, CCSG - CA023074]; American Heart Association [16PRE27500011]en
dc.language.isoenen
dc.publisherCOMPANY OF BIOLOGISTS LTDen
dc.relation.urlhttp://jcs.biologists.org/lookup/doi/10.1242/jcs.202572en
dc.rights© 2017. Published by The Company of Biologists Ltd.en
dc.subjectGap junctionen
dc.subjectConnexinen
dc.subjectCell cycleen
dc.subjectApoptosisen
dc.subjectGatingen
dc.subjectPhosphorylationen
dc.titleRegulation of Cx37 channel and growth-suppressive properties by phosphorylationen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Dept Physiolen
dc.identifier.journalJournal of Cell Scienceen
dc.description.note12 month embargo; Published online: 1 Oct 2017.en
dc.description.collectioninformationThis 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.en
dc.eprint.versionFinal published versionen
html.description.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.


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