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Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively regulates glucose-stimulated insulin secretion in pancreatic β-cells.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2012 Aug 31; Vol. 287 (36), pp. 30368-75. Date of Electronic Publication: 2012 Jul 13. - Publication Year :
- 2012
-
Abstract
- Brain-selective kinase 2 (BRSK2) has been shown to play an essential role in neuronal polarization. In the present study, we show that BRSK2 is also abundantly expressed in pancreatic islets and MIN6 β-cell line. Yeast two-hybrid screening, GST fusion protein pull-down, and co-immunoprecipitation assays reveal that BRSK2 interacts with CDK-related protein kinase PCTAIRE1, a kinase involved in neurite outgrowth and neurotransmitter release. In MIN6 cells, BRSK2 co-localizes with PCTAIRE1 in the cytoplasm and phosphorylates one of its serine residues, Ser-12. Phosphorylation of PCTAIRE1 by BRSK2 reduces glucose-stimulated insulin secretion (GSIS) in MIN6 cells. Conversely, knockdown of BRSK2 by siRNA increases serum insulin levels in mice. Our results reveal a novel function of BRSK2 in the regulation of GSIS in β-cells via a PCTAIRE1-dependent mechanism and suggest that BRSK2 is an attractive target for developing novel diabetic drugs.
- Subjects :
- Animals
Cell Line
Cyclin-Dependent Kinases genetics
Cytoplasm genetics
Cytoplasm metabolism
Gene Knockdown Techniques
Glucose genetics
Humans
Insulin genetics
Insulin Secretion
Insulin-Secreting Cells cytology
Male
Mice
Mice, Inbred BALB C
Phosphorylation physiology
Protein Serine-Threonine Kinases genetics
Cyclin-Dependent Kinases metabolism
Glucose metabolism
Insulin metabolism
Insulin-Secreting Cells metabolism
Protein Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 287
- Issue :
- 36
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 22798068
- Full Text :
- https://doi.org/10.1074/jbc.M112.375618