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 The Author(s). 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 email@example.com.
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]
- Serine 319 phosphorylation is necessary and sufficient to induce a Cx37 conformation that leads to arrested cell cycling.
- Authors: Taylor SZ, Jacobsen NL, Pontifex TK, Langlais P, Burt JM
- Issue date: 2020 Jun 18
- A functional channel is necessary for growth suppression by Cx37.
- Authors: Good ME, Nelson TK, Simon AM, Burt JM
- Issue date: 2011 Jul 15
- Carboxy terminus and pore-forming domain properties specific to Cx37 are necessary for Cx37-mediated suppression of insulinoma cell proliferation.
- Authors: Nelson TK, Sorgen PL, Burt JM
- Issue date: 2013 Dec 15
- Structural determinants and proliferative consequences of connexin 37 hemichannel function in insulinoma cells.
- Authors: Good ME, Ek-Vitorín JF, Burt JM
- Issue date: 2014 Oct 31
- Phosphorylation-Dependent Intra-Domain Interaction of the Cx37 Carboxyl-Terminus Controls Cell Survival.
- Authors: Jacobsen NL, Pontifex TK, Langlais PR, Burt JM
- Issue date: 2019 Feb 6