Ser279

Site Information
sSPtAPLsPMsPPGy SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448853

In vivo Characterization
Methods used to characterize site in vivo:	electrophoretic mobility shift ( 11 ) , immunoassay ( 2 , 8 ) , mass spectrometry ( 3 , 7 , 12 , 13 , 18 ) , mutation of modification site ( 6 , 11 ) , phospho-antibody ( 1 , 2 , 4 , 8 , 9 , 10 , 14 , 15 , 16 , 17 , 19 , 20 ) , western blotting ( 1 , 2 , 4 , 6 , 8 , 9 , 10 , 14 , 16 , 17 )
Disease tissue studied:	breast cancer ( 7 , 13 ) , HER2 positive breast cancer ( 3 ) , luminal A breast cancer ( 3 ) , luminal B breast cancer ( 3 ) , breast cancer, triple negative ( 3 ) , cervical cancer ( 19 ) , lung cancer ( 13 ) , non-small cell lung cancer ( 13 ) , neuroblastoma ( 12 ) , pancreatic cancer ( 8 ) , pancreatic carcinoma ( 8 )
Relevant cell line - cell type - tissue:	Aspc1 (pancreatic) ( 8 ) , astrocyte ( 16 ) , breast ( 3 ) , BT-549 (breast cell) ( 13 ) , BxPC-3 (pancreatic) ( 8 ) , Calu 6 (pulmonary) ( 13 ) , cervix ( 19 ) , CHO (fibroblast) ( 17 ) , E14tg2a ('stem, embryonic') ( 9 ) , endothelial ( 4 ) , H2009 (pulmonary) ( 13 ) , H2077 (pulmonary) ( 13 ) , H2887 (pulmonary) ( 13 ) , H322M (pulmonary) ( 13 ) , HeLa (cervical) ( 6 ) , HMLER ('stem, breast cancer') [CXCR4 (human), knockdown] ( 7 ) , HMLER ('stem, breast cancer') ( 7 ) , HPMEC (pulmonary) ( 1 ) , IMR32 (neural crest) ( 20 ) , Jurkat (T lymphocyte) ( 18 ) , keratinocyte-skin ( 15 ) , LA-25 (fibroblast) ( 2 ) , LOU-NH91 (squamous) ( 13 ) , MDA-MB-231 (breast cell) ( 13 ) , MDCK (epithelial) ( 17 ) , NB10 (neural crest) ( 12 ) , NCI-H1648 (pulmonary) ( 13 ) , NCI-H460 (pulmonary) ( 13 ) , NPC (neural crest) ( 12 ) , pancreas ( 8 ) , RALA255-10G (hepatocyte) ( 2 ) , uterine artery ( 4 ) , VSMC ('muscle, smooth') ( 14 )

Upstream Regulation
Regulatory protein:	GJA1 (human) ( 1 )
Putative in vivo kinases:	P38A (human) ( 15 )
Kinases, in vitro:	MAPKAPK2 (human) ( 11 )
Treatments:	ATP ( 4 ) , bafilomycin_A ( 2 ) , brefeldin_A ( 2 ) , cAMP_analog ( 14 ) , CXCL12 ( 7 ) , cycloheximide ( 2 ) , DADS ( 14 ) , EGF ( 6 , 9 ) , MG132 ( 2 ) , phorbol_ester ( 4 , 10 , 17 ) , PP2 ( 4 ) , pregnancy ( 4 ) , pressure ( 16 ) , SB202190 ( 15 ) , SB203580 ( 15 ) , sulforaphane ( 8 ) , U0126 ( 4 , 16 ) , UV ( 15 ) , vanadate ( 2 ) , VEGF ( 4 )

Downstream Regulation
Effects of modification on GJA1:	activity, inhibited ( 4 ) , intracellular localization ( 1 , 19 ) , molecular association, regulation ( 9 ) , protein conformation ( 11 ) , protein degradation ( 6 , 15 ) , protein stabilization ( 8 ) , ubiquitination ( 6 )
Effects of modification on biological processes:	apoptosis, induced ( 8 ) , carcinogenesis, induced ( 1 ) , carcinogenesis, inhibited ( 8 ) , cell growth, induced ( 1 ) , cell growth, inhibited ( 14 ) , cell motility, induced ( 1 ) , cytoskeletal reorganization ( 2 , 15 ) , endocytosis, induced ( 9 ) , signaling pathway regulation ( 4 )
Induce interaction with:	CLTA (human) ( 9 )

Disease / Diagnostics Relevance
Relevant diseases:	cervical cancer ( 19 ) , pancreatic ductal adenocarcinoma ( 8 )

References
1	Zhou Z, et al. (2022) Connexin 43 overexpression induces lung cancer angiogenesis following phosphorylation at Ser279 in its C-terminus. Oncol Lett 24, 293 35949588 Curated Info
2	Solan JL, Lampe PD (2020) Src Regulation of Cx43 Phosphorylation and Gap Junction Turnover. Biomolecules 10 33255329 Curated Info
3	Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62 27251275 Curated Info
4	Boeldt DS, et al. (2015) Phosphorylation of Ser-279/282 and Tyr-265 positions on Cx43 as possible mediators of VEGF-165 inhibition of pregnancy-adapted Ca2+ burst function in ovine uterine artery endothelial cells. Mol Cell Endocrinol 412, 73-84 26033246 Curated Info
5	Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704 24719451 Curated Info
6	Schmitt M, et al. (2014) Mutation of human connexin43 amino acids s279/s282 increases protein stability upon treatment with epidermal growth factor. Cell Biochem Biophys 69, 379-84 24399133 Curated Info
7	Yi T, et al. (2014) Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells. Proc Natl Acad Sci U S A 111, E2182-90 24782546 Curated Info
8	Forster T, et al. (2014) Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication. Oncotarget 5, 1621-34 24742583 Curated Info
9	Fong JT, Nimlamool W, Falk MM (2014) EGF induces efficient Cx43 gap junction endocytosis in mouse embryonic stem cell colonies via phosphorylation of Ser262, Ser279/282, and Ser368. FEBS Lett 588, 836-44 24492000 Curated Info
10	Dunn CA, Lampe PD (2014) Injury-triggered Akt phosphorylation of Cx43: a ZO-1-driven molecular switch that regulates gap junction size. J Cell Sci 127, 455-64 24213533 Curated Info
11	Grosely R, et al. (2013) Effects of Phosphorylation on the Structure and Backbone Dynamics of the Intrinsically Disordered Connexin43 C-terminal Domain. J Biol Chem 288, 24857-70 23828237 Curated Info
12	DeNardo BD, et al. (2013) Quantitative phosphoproteomic analysis identifies activation of the RET and IGF-1R/IR signaling pathways in neuroblastoma. PLoS One 8, e82513 24349301 Curated Info
13	Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68 22617229 Curated Info
14	Joshi CN, et al. (2012) Control of vascular smooth muscle cell growth by connexin 43. Front Physiol 3, 220 22737133 Curated Info
15	Bellei B, et al. (2008) Ultraviolet A induced modulation of gap junctional intercellular communication by P38 MAPK activation in human keratinocytes. Exp Dermatol 17, 115-24 18047584 Curated Info
16	Malone P, et al. (2007) Pressure induces loss of gap junction communication and redistribution of connexin 43 in astrocytes. Glia 55, 1085-98 17551925 Curated Info
17	Solan JL, Lampe PD (2007) Key connexin 43 phosphorylation events regulate the gap junction life cycle. J Membr Biol 217, 35-41 17629739 Curated Info
18	Possemato A (2007) CST Curation Set: 2928; Year: 2007; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
19	Steinhoff I, et al. (2006) Phosphorylation of the gap junction protein Connexin43 in CIN III lesions and cervical carcinomas. Cancer Lett 235, 291-7 15958277 Curated Info
20	Arnold JM, Phipps MW, Chen J, Phipps J (2005) Cellular sublocalization of Cx43 and the establishment of functional coupling in IMR-32 neuroblastoma cells. Mol Carcinog 42, 159-69 15605363 Curated Info