CaMKK2 is inactivated by cAMP-PKA signaling and 14-3-3 adaptor proteins
Christopher G Langendorf, Matthew T O'Brien, Kevin RW Ngoei, Luke M McAloon, Urmi Dhagat, Ashfaqul Hoque, Naomi XY Ling, Toby A Dite, Sandra Galic, Kim Loh, Michael W Parker, Jonathan S Oakhill, Bruce E Kemp, John W Scott
JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2020
The calcium-calmodulin-dependent protein kinase kinase-2 (CaMKK2) is a key regulator of cellular and whole-body energy metabolism. It is known to be activated by increases in intracellular Ca2+, but the mechanisms by which it is inactivated are less clear. CaMKK2 inhibition protects against prostate cancer, hepatocellular carcinoma, and metabolic derangements induced by a high-fat diet; therefore, elucidating the intracellular mechanisms that inactivate CaMKK2 has important therapeutic implications. Here we show that stimulation of cAMP-dependent protein kinase A (PKA) signaling in cells inactivates CaMKK2 by phosphorylation of three conserved serine residues. PKA-dependent phosphorylation o..View full abstract
Awarded by National Health and Medical Research Council
Awarded by Jack Brockhoff Foundation
Awarded by Australian Research Council
This work was supported by National Health and Medical Research Council Grants 1138102 (to J. W. S.) and 1145265 (to J. S. O.) and the Jack Brockhoff Foundation Grant JBF-4206, 2016 (to C. G. L.). C. G. L. is a National Health and Medical Research Council Early Career Research Fellow and M. W. P. a National Health and Medical Research Council Senior Principal Research Fellow. B. E. K. was a National Health and Medical Research Council Fellow supported by the Australian Research Council (DP170101196). This project was supported in part by the Victorian Government's Operational Infrastructure Support Program. MS data were acquired at the Mass Spectrometry and Proteomics Facility, Bio21, University of Melbourne. We acknowledge the funding support of the Australian Cancer Research Foundation toward the ACRF Rational Drug Discovery Centre.