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| Status |
Public on Feb 13, 2019 |
| Title |
GLP-1 signaling suppresses menin's transcriptional block by phosphorylation in beta cells |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
We find that GLP-1 signaling-activated PKA directly phosphorylates menin at serine 487 residue, relieving menin mediated suppression of insulin expression in beta cells and islets of diabetic GK rat. Mechanistically, GLP-1-induced PKA activation leads to menin Ser487 phosphorylation, and phosphorylated menin gains increased binding affinity to cytoskeleton proteins such as beta actin and myosin. Sequestration of Ser487 phosphorylated menin from the Ins1 gene promoter leads to reduced binding of menin-associating repressive epigenetic regulators such as SUV39H1 and HDAC1 at the locus, resulting in increased Ins1 transcription. Our results have linked GLP-1 signaling to physiologically suppression of menin function in repressing insulin expression, and uncovered a potential step to modulate menin phosphorylation to improve T2D therapy.
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| Overall design |
mRNA profiles of INS-1 cells overexpressing menin S487A or S487D mutant were generated by deep sequencing, in triplicate.
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| Contributor(s) |
Xing B |
| Citation missing |
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| |
| Submission date |
Nov 07, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Bowen Xing |
| E-mail(s) |
bwxing@whu.edu.cn
|
| Phone |
86-13005411156
|
| Organization name |
Shenzhen University
|
| Street address |
Nanhai Street 3688
|
| City |
Shenzhen |
| State/province |
Guangdong |
| ZIP/Postal code |
518060 |
| Country |
China |
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| Platforms (1) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA417512 |
| SRA |
SRP124536 |
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