Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively regulates glucose-stimulated insulin secretion in pancreatic β-cells

Xin Ya Chen, Xiu Ting Gu, Hexige Saiyin, Bo Wan, Yu Jing Zhang, Jing Li, Ying Li Wang, Rui Gao, Yu Fan Wang, Wei Ping Dong, Sonia M. Najjar, Chen Yu Zhang, Han Fei Ding, Jun O. Liu, Long Yu

Research output: Contribution to journalArticle

25 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)30368-30375
Number of pages8
JournalJournal of Biological Chemistry
Volume287
Issue number36
DOIs
StatePublished - Aug 31 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Chen, X. Y., Gu, X. T., Saiyin, H., Wan, B., Zhang, Y. J., Li, J., Wang, Y. L., Gao, R., Wang, Y. F., Dong, W. P., Najjar, S. M., Zhang, C. Y., Ding, H. F., Liu, J. O., & Yu, L. (2012). Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively regulates glucose-stimulated insulin secretion in pancreatic β-cells. Journal of Biological Chemistry, 287(36), 30368-30375. https://doi.org/10.1074/jbc.M112.375618