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.
Highlights
Brain-selective kinase 2 (BRSK2) has never reported to be functional in pancreatic islets
Yeast two-hybrid screening, GST fusion protein pull-down, and co-immunoprecipitation assays reveal that BRSK2 interacts with cyclin-dependent kinase (CDK)-related protein kinase PCTAIRE1, a kinase involved in neurite outgrowth and neurotransmitter release
Our results reveal a novel function of BRSK2 in the regulation of glucose-stimulated insulin secretion (GSIS) in -cells via a PCTAIRE1dependent mechanism and suggest that BRSK2 is an attractive target for developing novel diabetic drugs
Summary
BRSK2 has never reported to be functional in pancreatic islets. Results: BRSK2 interacts with PCTAIRE1 and phosphorylates it at Ser-12. Significance: This study reveals a novel function of BRSK2 in insulin secretion and uncovers its related regulation mechanism. Phosphorylation of PCTAIRE1 by BRSK2 reduces glucose-stimulated insulin secretion (GSIS) in MIN6 cells. BRSK2 and closely-related BRSK1 ( named SAD-B) are orthologs of SAD-1 in Caenorhabditis elegans [2, 3] They were originally identified as genes expressed in the brain, with an essential function in neuronal polarization [2]. BRSK2 Regulates Insulin Secretion in  Cells branch of the cyclin-dependent kinase (CDK) family, PCTAIRE1 has two isoforms in higher organisms, PCTAIRE2 and PCTAIRE3 [17], both of which contain a large N-terminal domain. We uncovered new functions of BRSK2 and PCTAIRE1 in pancreatic -cells We demonstrated that both kinases are highly expressed in human pancreatic islets and MIN6 murine -cell line. We found that PCTAIRE1 is a substrate of BRSK2 and the phosphorylation of PCTAIRE1 by BRSK2 plays a crucial role in regulating insulin secretion in response to glucose
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
