Journal article

Functional analysis of an R311C variant of Ca2 -calmodulin-dependent protein kinase kinase-2 (CaMKK2) found as a de novo mutation in a patient with bipolar disorder

Naomi XY Ling, Christopher G Langendorf, Ashfaqul Hoque, Sandra Galic, Kim Loh, Bruce E Kemp, Andrew L Gundlach, Jonathan S Oakhill, John W Scott

BIPOLAR DISORDERS | WILEY | Published : 2020


OBJECTIVES: Loss-of-function mutations in the gene encoding the calcium-calmodulin (Ca2+ -CaM)-dependent protein kinase kinase-2 (CaMKK2) enzyme are linked to bipolar disorder. Recently, a de novo arginine to cysteine (R311C) mutation in CaMKK2 was identified from a whole exome sequencing study of bipolar patients and their unaffected parents. The aim of the present study was to determine the functional consequences of the R311C mutation on CaMKK2 activity and regulation by Ca2+ -CaM. METHODS: The effects of the R311C mutation on CaMKK2 activity and Ca2+ -CaM activation were examined using a radiolabeled adenosine triphosphate (ATP) kinase assay. We performed immunoblot analysis to determine..

View full abstract


Awarded by National Health and Medical Research Council

Awarded by Jack Brockhoff Foundation

Funding Acknowledgements

National Health and Medical Research Council, Grant/Award Number: 1138102 and 1145265; Jack Brockhoff Foundation, Grant/Award Number: JBF-4206; Victorian Government's Operational Infrastructure