Phosphorylation-Dependent Intra-Domain Interaction of the Cx37 Carboxyl-Terminus Controls Cell Survival
dc.contributor.author | Jacobsen, Nicole L | |
dc.contributor.author | Pontifex, Tasha K | |
dc.contributor.author | Langlais, Paul R | |
dc.contributor.author | Burt, Janis M | |
dc.date.accessioned | 2019-07-08T17:20:15Z | |
dc.date.available | 2019-07-08T17:20:15Z | |
dc.date.issued | 2019-02-06 | |
dc.identifier.citation | Jacobsen NL, Pontifex TK, Langlais PR, Burt JM. Phosphorylation-Dependent Intra-Domain Interaction of the Cx37 Carboxyl-Terminus Controls Cell Survival. Cancers. 2019; 11(2):188. | en_US |
dc.identifier.issn | 2072-6694 | |
dc.identifier.pmid | 30736283 | |
dc.identifier.doi | 10.3390/cancers11020188 | |
dc.identifier.uri | http://hdl.handle.net/10150/633329 | |
dc.description.abstract | Differential phosphorylation of the carboxyl-terminus of connexin 37 (Cx37-CT) regulates phenotypic switching between cell growth phenotypes (cell death, cell cycle arrest, proliferation). The specific phosphorylation events in the Cx37-CT that are necessary for these growth regulatory effects are currently unknown. Through the combined use of deletion and site specific (de)phospho-mimetic Cx37-CT mutants, our data suggest a phosphorylation-dependent interaction between the mid-tail (aa 273-317) and end-tail (aa 318-333) portions of the Cx37-CT that regulates cell survival. As detected by mass spectrometry, Cx37 was phosphorylated at serines 275, 321, and 328; phosphomimetic mutations of these sites resulted in cell death when expressed in rat insulinoma cells. Alanine substitution at S328, but not at S275 or S321, also triggered cell death. Cx37-S275D uniquely induced the death of only low density, non-contact forming cells, but neither hemichannel open probability nor channel conductance distinguished death-inducing mutants. As channel function is necessary for cell death, together the data suggest that the phosphorylation state of the Cx37-CT controls an intra-domain interaction within the CT that modifies channel function and induces cell death. | en_US |
dc.description.sponsorship | National Institutes of Health [HL056732, HL131712, DK098493, HL007249]; American Heart Association [16PRE2750011] | en_US |
dc.language.iso | en | en_US |
dc.publisher | MDPI | en_US |
dc.relation.url | https://www.mdpi.com/2072-6694/11/2/188 | en_US |
dc.rights | © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | cell cycle | en_US |
dc.subject | cell death | en_US |
dc.subject | connexin | en_US |
dc.subject | gap junction | en_US |
dc.subject | gating | en_US |
dc.subject | phosphorylation | en_US |
dc.title | Phosphorylation-Dependent Intra-Domain Interaction of the Cx37 Carboxyl-Terminus Controls Cell Survival | en_US |
dc.type | Article | en_US |
dc.contributor.department | Univ Arizona, Dept Physiol | en_US |
dc.contributor.department | Univ Arizona, Dept Med | en_US |
dc.identifier.journal | CANCERS | en_US |
dc.description.note | Open access journal | en_US |
dc.description.collectioninformation | 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. | en_US |
dc.eprint.version | Final published version | en_US |
dc.source.journaltitle | Cancers | |
refterms.dateFOA | 2019-07-08T17:20:15Z |