PXD012191

PXD012191 is an original dataset announced via ProteomeXchange.

Title	Cx37 Phosphorylation and cell cycle regulation
Description	Using alanine and aspartate substitutions to mimic dephosphorylated and phosphorylated Cx37, respectively, we showed that induced expression of Cx37 in rat insulinoma cells could arrest cell cycle progression, support cell cycle progression or cause cell death in a phosphosite specific manner. In the current study, we induced Cx37 expression for 24h in 80-90% confluent Rin cells, which arrests their proliferation for many days, and determined by mass spectrometry which sites in Cx37 were phosphorylated under control conditions, following stimulation of PKC with phorbol ester, or following inhibition of PKC with bis-indolylmaleimide. The results consistently showed phosphorylation of serine 319, a high probability target for CMGC kinases. Serines 275, 321 and 328 were also identified as phosphorylated residues; these sites are also high probability targets of growth factor activated kinases. No quantitative differences between treatment groups were identified. Since growth arrest was the phenotype displayed by the cells from which the Cx37 isolated, it seems likely that S319, when phosphorylated, promotes growth arrest. Single site mutations of Serines 275, 321 and 328 also alter growth phenotype: S275D induces cell death at low cell densities but has no detectable effect on Rin cell proliferation at high cell densities; S321D induces cell death at all cell densities; and both S328A and S238D induce cell death at all densities. These results support the conclusion that Cx37 regulates growth phenotype in a phosphorylation-site specific manner and suggest that intra-molecular interactions are modulated by differential phosphorylation in the carboxy terminal domain.
HostingRepository	PRIDE
AnnounceDate	2019-02-13
AnnouncementXML	Submission_2019-02-13_05:12:08.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD012191
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Paul Langlais
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Ammonia-loss; Phospho; Dehydrated; Oxidation; Acetyl
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-24 02:56:04	ID requested
⏵ 1	2019-02-13 05:12:10	announced

Jacobsen NL, Pontifex TK, Langlais PR, Burt JM, Phosphorylation-Dependent Intra-Domain Interaction of the Cx37 Carboxyl-Terminus Controls Cell Survival. Cancers (Basel), 11(2):(2019) [pubmed]

submitter keyword: gap junction

Growth arrest

proliferation

cell death

differential phosphorylation

Paul R. Langlais
contact affiliation	Department of Medicine, Division of Endocrinology, University of Arizona College of Medicine
contact email	langlais@deptofmed.arizona.edu
lab head
Paul Langlais
contact affiliation	University of Arizona
contact email	langlais@deptofmed.arizona.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012191
     1. Label: PRIDE project
     2. Name: Cx37 Phosphorylation and cell cycle regulation