| RRC ID |
58276
|
| Author |
Sugimoto K, Ichikawa-Tomikawa N, Kashiwagi K, Endo C, Tanaka S, Sawada N, Watabe T, Higashi T, Chiba H.
|
| Title |
Cell adhesion signals regulate the nuclear receptor activity.
|
| Journal |
Proc Natl Acad Sci U S A
|
| Abstract |
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.
|
| Volume |
116(49)
|
| Pages |
24600-24609
|
| Published |
2019-12-3
|
| DOI |
10.1073/pnas.1913346116
|
| PII |
1913346116
|
| PMID |
31740618
|
| PMC |
PMC6900646
|
| MeSH |
Animals
Cell Adhesion / physiology*
Cell Line
Claudins / genetics
Claudins / metabolism*
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
Receptors, Retinoic Acid / metabolism
Signal Transduction
Tyrosine / genetics
src-Family Kinases / metabolism
|
| IF |
9.412
|
| Times Cited |
0
|
| Resource |
| DNA material |
CSII-EF-MCS-IRES2-Venus (RDB04384)
pCMV-VSV-G-RSV-Rev (RDB04393) |
| Human and Animal Cells |
BRC4(AES0008) |
