Ser368
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Home > Phosphorylation Site Page: > Ser368  -  GJA1 (human)

Site Information
QRPssRAssRAssRP   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447813

In vivo Characterization
Methods used to characterize site in vivo:
electrophoretic mobility shift ( 13 ) , flow cytometry ( 3 ) , immunoassay ( 1 , 2 , 6 , 11 ) , mutation of modification site ( 1 , 6 , 13 , 14 , 17 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 15 , 16 , 17 , 18 , 19 ) , western blotting ( 1 , 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 14 , 15 , 16 , 17 , 18 )
Disease tissue studied:
pancreatic cancer ( 11 ) , pancreatic carcinoma ( 11 )
Relevant cell line - cell type - tissue:
'muscle, smooth'-'heart, artery' ( 7 ) , 3T3 (fibroblast) ( 14 ) , Aspc1 (pancreatic) ( 11 ) , BxPC-3 (pancreatic) ( 11 ) , CHO (fibroblast) ( 18 ) , E.coli (bacterial) ( 1 ) , E14tg2a ('stem, embryonic') ( 12 ) , endothelial ( 8 ) , granulosa ( 2 ) , H9c2 (myoblast) ( 3 ) , HaCaT (keratinocyte) ( 1 ) , HEGCs ( 10 ) , HEK293T (epithelial) ( 1 ) , HeLa (cervical) ( 17 ) , HESCs (endometrial) ( 10 ) , HMEC (endothelial) ( 9 , 16 ) , HPMEC (pulmonary) ( 4 ) , keratinocyte ( 19 ) , LA-25 (fibroblast) ( 5 ) , MDCK (epithelial) ( 6 , 18 ) , MEF (fibroblast) ( 1 ) , pancreas ( 11 ) , skin ( 1 ) , uterine artery ( 8 ) , VSMC ('muscle, smooth') ( 15 )

Upstream Regulation
Regulatory protein:
EGFR (human) ( 2 ) , GJA1 (human) ( 4 ) , HER4 (human) ( 2 ) , HSP70 (human) ( 9 )
Putative in vivo kinases:
PKCA (human) ( 6 ) , PKCE (human) ( 19 ) , PRKD1 (human) ( 1 )
Kinases, in vitro:
PKCA (human) ( 13 ) , PKCE (human) ( 19 ) , PRKD1 (human) ( 1 )
Treatments:
AG1478 ( 2 ) , AMP-PNP ( 17 ) , ATP ( 8 ) , bafilomycin_A ( 5 ) , betacellulin ( 2 ) , BIO ( 11 ) , bisindolylmaleimide ( 19 ) , brefeldin_A ( 5 ) , CAIP ( 7 ) , chelerythrine ( 7 ) , ciclosporin ( 7 ) , CRT0066101 ( 1 ) , DADS ( 15 ) , EGF ( 12 ) , GF109203X ( 6 ) , Go_6976 ( 19 ) , hypoxia ( 16 ) , levonorgestrel/norgestrel ( 10 ) , low Na ( 7 ) , MG132 ( 5 ) , phorbol_ester ( 1 , 6 , 8 , 18 ) , PP2 ( 8 ) , Ro31-8220 ( 19 ) , simvastatin ( 3 ) , siRNA ( 1 ) , sotrastaurin ( 2 ) , SP600125 ( 11 ) , staurosporine ( 11 ) , sulforaphane ( 11 ) , tautomycin ( 7 ) , Tyrode's ( 7 ) , U0126 ( 2 , 8 ) , VEGF ( 8 ) , wounding ( 1 , 19 )

Downstream Regulation
Effects of modification on GJA1:
activity, induced ( 6 ) , activity, inhibited ( 17 ) , intracellular localization ( 1 , 2 ) , molecular association, regulation ( 12 ) , protein conformation ( 6 , 13 ) , protein degradation ( 1 ) , protein stabilization ( 11 ) , receptor internalization, induced ( 1 )
Effects of modification on biological processes:
apoptosis, induced ( 11 ) , carcinogenesis, inhibited ( 11 ) , cell motility, altered ( 19 ) , cell motility, induced ( 1 ) , endocytosis, induced ( 12 )
Induce interaction with:
CLTA (human) ( 12 )

Disease / Diagnostics Relevance
Relevant diseases:
pancreatic ductal adenocarcinoma ( 11 )

References 

1

Pun R, et al. (2024) PKCĪ¼ promotes keratinocyte cell migration through Cx43 phosphorylation-mediated suppression of intercellular communication. iScience 27, 109033
38375220   Curated Info

2

Li Y, et al. (2023) Betacellulin regulates gap junction intercellular communication by inducing the phosphorylation of connexin 43 in human granulosa-lutein cells. J Ovarian Res 16, 103
37231448   Curated Info

3

Pecoraro M, et al. (2023) Simvastatin Reduces Doxorubicin-Induced Cardiotoxicity: Effects beyond Its Antioxidant Activity. Int J Mol Sci 24
37108737   Curated Info

4

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

5

Solan JL, Lampe PD (2020) Src Regulation of Cx43 Phosphorylation and Gap Junction Turnover. Biomolecules 10
33255329   Curated Info

6

Cotter ML, et al. (2019) The lipidated connexin mimetic peptide, SRPTEKT-, is a potent inhibitor of Cx43 channels with specificity for the pS368 phospho-isoform. Am J Physiol Cell Physiol
31365296   Curated Info

7

Jabr RI, et al. (2016) Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction. Pflugers Arch 468, 1945-1955
27757582   Curated Info

8

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

9

Thuringer D, et al. (2015) Oncogenic extracellular HSP70 disrupts the gap-junctional coupling between capillary cells. Oncotarget 6, 10267-83
25868858   Curated Info

10

Zhao X, et al. (2015) Levonorgestrel Inhibits Human Endometrial Cell Proliferation through the Upregulation of Gap Junctional Intercellular Communication via the Nuclear Translocation of Ser255 Phosphorylated Cx43. Biomed Res Int 2015, 758684
26161412   Curated Info

11

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

12

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

13

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

14

Ahmad Waza A, Andrabi K, Ul Hussain M (2012) Adenosine-triphosphate-sensitive K+ channel (Kir6.1): a novel phosphospecific interaction partner of connexin 43 (Cx43). Exp Cell Res 318, 2559-66
22960107   Curated Info

15

Joshi CN, et al. (2012) Control of vascular smooth muscle cell growth by connexin 43. Front Physiol 3, 220
22737133   Curated Info

16

Faigle M, et al. (2008) ATP release from vascular endothelia occurs across Cx43 hemichannels and is attenuated during hypoxia. PLoS One 3, e2801
18665255   Curated Info

17

Lurtz MM, Louis CF (2007) Purinergic receptor-mediated regulation of lens connexin43. Invest Ophthalmol Vis Sci 48, 4177-86
17724204   Curated Info

18

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

19

Richards TS, et al. (2004) Protein kinase C spatially and temporally regulates gap junctional communication during human wound repair via phosphorylation of connexin43 on serine368. J Cell Biol 167, 555-62
15534005   Curated Info

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