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Protein Kinase CK2 Controls CaV2.1-Dependent Calcium Currents and Insulin Release in Pancreatic ?-Cells.


ABSTRACT: The regulation of insulin biosynthesis and secretion in pancreatic ?-cells is essential for glucose homeostasis in humans. Previous findings point to the highly conserved, ubiquitously expressed serine/threonine kinase CK2 as having a negative regulatory impact on this regulation. In the cell culture model of rat pancreatic ?-cells INS-1, insulin secretion is enhanced after CK2 inhibition. This enhancement is preceded by a rise in the cytosolic Ca2+ concentration. Here, we identified the serine residues S2362 and S2364 of the voltage-dependent calcium channel CaV2.1 as targets of CK2 phosphorylation. Furthermore, co-immunoprecipitation experiments revealed that CaV2.1 binds to CK2 in vitro and in vivo. CaV2.1 knockdown experiments showed that the increase in the intracellular Ca2+ concentration, followed by an enhanced insulin secretion upon CK2 inhibition, is due to a Ca2+ influx through CaV2.1 channels. In summary, our results point to a modulating role of CK2 in the CaV2.1-mediated exocytosis of insulin.

SUBMITTER: Scheuer R 

PROVIDER: S-EPMC7370021 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Protein Kinase CK2 Controls Ca<sub>V</sub>2.1-Dependent Calcium Currents and Insulin Release in Pancreatic β-Cells.

Scheuer Rebecca R   Philipp Stephan Ernst SE   Becker Alexander A   Nalbach Lisa L   Ampofo Emmanuel E   Montenarh Mathias M   Götz Claudia C  

International journal of molecular sciences 20200630 13


The regulation of insulin biosynthesis and secretion in pancreatic β-cells is essential for glucose homeostasis in humans. Previous findings point to the highly conserved, ubiquitously expressed serine/threonine kinase CK2 as having a negative regulatory impact on this regulation. In the cell culture model of rat pancreatic β-cells INS-1, insulin secretion is enhanced after CK2 inhibition. This enhancement is preceded by a rise in the cytosolic Ca<sup>2+</sup> concentration. Here, we identified  ...[more]

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