Cell adhesion signals regulate the nuclear receptor activity.
Animals
Cell Adhesion
/ physiology
Cell Line
Claudins
/ genetics
Estrogen Receptor alpha
/ metabolism
Gene Expression Regulation
Humans
Mice
Mutation
Phosphatidylinositol 3-Kinases
/ metabolism
Phosphorylation
Protein Domains
Proto-Oncogene Proteins c-akt
/ metabolism
Receptors, Cytoplasmic and Nuclear
/ metabolism
Receptors, Retinoic Acid
/ genetics
Signal Transduction
Tyrosine
/ genetics
src-Family Kinases
/ metabolism
Retinoic Acid Receptor gamma
claudin
estrogen receptor
retinoic acid receptor
signal transduction
tight junction
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
03 12 2019
03 12 2019
Historique:
pubmed:
20
11
2019
medline:
14
4
2020
entrez:
20
11
2019
Statut:
ppublish
Résumé
Cell adhesion is essential for proper tissue architecture and function in multicellular organisms. Cell adhesion molecules not only maintain tissue integrity but also possess signaling properties that contribute to diverse cellular events such as cell growth, survival, differentiation, polarity, and migration; however, the underlying molecular basis remains poorly defined. Here we identify that the cell adhesion signal initiated by the tight-junction protein claudin-6 (CLDN6) regulates nuclear receptor activity. We show that CLDN6 recruits and activates Src-family kinases (SFKs) in second extracellular domain-dependent and Y196/200-dependent manners, and SFKs in turn phosphorylate CLDN6 at Y196/200. We demonstrate that the CLDN6/SFK/PI3K/AKT axis targets the AKT phosphorylation sites in the retinoic acid receptor γ (RARγ) and the estrogen receptor α (ERα) and stimulates their activities. Interestingly, these phosphorylation motifs are conserved in 14 of 48 members of human nuclear receptors. We propose that a similar link between diverse cell adhesion and nuclear receptor signalings coordinates a wide variety of physiological and pathological processes.
Identifiants
pubmed: 31740618
pii: 1913346116
doi: 10.1073/pnas.1913346116
pmc: PMC6900646
doi:
Substances chimiques
Claudins
0
ESR1 protein, human
0
Estrogen Receptor alpha
0
Receptors, Cytoplasmic and Nuclear
0
Receptors, Retinoic Acid
0
Tyrosine
42HK56048U
src-Family Kinases
EC 2.7.10.2
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
claudin 6
MRC5FX426I
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
24600-24609Déclaration de conflit d'intérêts
The authors declare no competing interest.
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