Systemic ablation of Camkk2 impairs metastatic colonization and improves insulin sensitivity in TRAMP mice : Evidence for cancer cell-extrinsic CAMKK2 functions in prostate cancer

Journal article

Pulliam, Thomas L., Awad, Dominik, Han, Jenny J., Murray, Mollianne M., Ackroyd, Jeffrey J., Goli, Pavithr, Oakhill, Jonathan S., Scott, John W., Ittmann, Michael M. and Frigo, Daniel E.. (2022). Systemic ablation of Camkk2 impairs metastatic colonization and improves insulin sensitivity in TRAMP mice : Evidence for cancer cell-extrinsic CAMKK2 functions in prostate cancer. Cells. 11(12), p. Article 1890. https://doi.org/10.3390/cells11121890
AuthorsPulliam, Thomas L., Awad, Dominik, Han, Jenny J., Murray, Mollianne M., Ackroyd, Jeffrey J., Goli, Pavithr, Oakhill, Jonathan S., Scott, John W., Ittmann, Michael M. and Frigo, Daniel E.
Abstract

Despite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2’s effects on whole-body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of Camkk2 slows, but does not stop, primary prostate tumorigenesis in the TRansgenic Adenocarcinoma Mouse Prostate (TRAMP) genetic mouse model. Consistent with prior epidemiological reports supporting a link between obesity and prostate cancer aggressiveness, TRAMP mice fed a high-fat diet exhibited a pronounced increase in the colonization of lung metastases. We demonstrated that this effect on the metastatic spread was dependent on CAMKK2. Notably, diet-induced lung metastases exhibited a highly aggressive neuroendocrine phenotype. Concurrently, Camkk2 deletion improved insulin sensitivity in the same mice. Histological analyses revealed that cancer cells were smaller in the TRAMP;Camkk2−/− mice compared to TRAMP;Camkk2+/+ controls. Given the differences in circulating insulin levels, a known regulator of cell growth, we hypothesized that systemic CAMKK2 could promote prostate cancer cell growth and disease progression in part through cancer cell-extrinsic mechanisms. Accordingly, host deletion of Camkk2 impaired the growth of syngeneic murine prostate tumors in vivo, confirming nonautonomous roles for CAMKK2 in prostate cancer. Cancer cell size and mTOR signaling was diminished in tumors propagated in Camkk2-null mice. Together, these data indicate that, in addition to cancer cell-intrinsic roles, CAMKK2 mediates prostate cancer progression via tumor-extrinsic mechanisms. Further, we propose that CAMKK2 inhibition may also help combat common metabolic comorbidities in men with advanced prostate cancer.

Keywordsprostate cancer; CAMKK2; obesity; metastasis; TRAMP; high-fat diet; insulin; mTOR; neuroendocrine prostate cancer (NEPC)
Year2022
JournalCells
Journal citation11 (12), p. Article 1890
PublisherMDPI AG
Multidisciplinary Digital Publishing Institute (MDPI AG)
ISSN2073-4409
Digital Object Identifier (DOI)https://doi.org/10.3390/cells11121890
PubMed ID35741020
Scopus EID2-s2.0-85132686318
PubMed Central IDPMC9221545
Open accessPublished as ‘gold’ (paid) open access
Page range1-19
FunderNational Institutes of Health (NIH), United States of America
American Cancer Society
Mike Slive Foundation for Prostate Cancer Research
National Health and Medical Research Council (NHMRC)
American Legion Auxiliary
MD Anderson Cancer Center (MDACC)
Baylor College of Medicine
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online10 Jun 2022
Publication process dates
Accepted07 Jun 2022
Deposited01 Mar 2023
Grant IDNIHR01CA184208
P50CA140388
RSG-16-084-01-TBE
GNT1138102
GNT1145265
P30CA016672
UM1HG006348
R01DK114356
R01HL130249
Permalink -

https://acuresearchbank.acu.edu.au/item/8yw33/systemic-ablation-of-camkk2-impairs-metastatic-colonization-and-improves-insulin-sensitivity-in-tramp-mice-evidence-for-cancer-cell-extrinsic-camkk2-functions-in-prostate-cancer

Log in to edit

Download files

Publisher's version
OA_Pulliam_2022_Systemic_ablation_of_Camkk2_impairs_metastatic.pdf
License: CC BY 4.0
File access level: Open

  • 61
    total views
  • 35
    total downloads
  • 4
    views this month
  • 0
    downloads this month
These values are for the period from 19th October 2020, when this repository was created.

Export as

Related outputs

The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury
Katerelos, Marina, Gleich, Kurt, Harley, Geoff, Loh, Kim, Oakhill, Jonathan, Kemp, Bruce Ernest, De Souza, David P., Narayana, Vinod K., Coughlan, Melinda T., Laskowski, Adrienne, Ling, Naomi, Murray-Segal, Lisa, Brink, Robert, Lee, Mardiana, Power, David and Mount, Peter. (2024). The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury. Biomedicine and Pharmacotherapy. 175, pp. 116730-116742. https://doi.org/10.1016/j.biopha.2024.116730
AMPK protects endothelial cells against HSV-1 replication via inhibition of mTORC1 and ACC1
Doshi, Heena, Spengler, Katrin, Godbole, Amod, Gee, Yi Sing, Baell, Jonathan B., Oakhill, Jonathan, Henke, Andreas and Heller, Regine. (2023). AMPK protects endothelial cells against HSV-1 replication via inhibition of mTORC1 and ACC1. Microbiology Spectrum. 11(5), pp. 1-22. https://doi.org/10.1128/spectrum.00417-23
SGC-CAMKK2-1 : A chemical probe for CAMKK2
Wells, Carrow, Liang, Yi, Pulliam, Thomas L., Lin, Chenchu, Awad, Dominik, Eduful, Benjamin, O’Byrne, Sean, Hossain, Mohammad Anwar, Catta-Preta, Carolina Moura Costa, Ramos, Priscila Zonzini, Gileadi, Opher, Gileadi, Carina, Couñago, Rafael M., Stork, Brittany, Langendorf, Christopher G., Nay, Kevin, Oakhill, Jonathan S., Mukherjee, Debarati, Racioppi, Luigi, ... Drewry, David H.. (2023). SGC-CAMKK2-1 : A chemical probe for CAMKK2. Cells. 12(2), p. Article 287. https://doi.org/10.3390/cells12020287
Elevated basal AMP-activated protein kinase activity sensitizes colorectal cancer cells to growth inhibition by metformin
Morrison, Kaitlin R., Wang, Tingting, Chan, Kuan Yoow, Trotter, Eleanor W., Gillespie, Ari, Michael, Michael Z., Oakhill, Jonathan S., Hagan, Iain M. and Petersen, Janni. (2023). Elevated basal AMP-activated protein kinase activity sensitizes colorectal cancer cells to growth inhibition by metformin. Open Biology. 13(4), p. Article 230021. https://doi.org/10.1098/rsob.230021
Neuropeptide Y1 receptor antagonism protects β-cells and improves glycemic control in type 2 diabetes
Yang, Chieh-Hsin, Ann-Onda, Danise, Lin, Xushu, Fynch, Stacey, Nadarajah, Shaktypreya, Pappas, Evan G., Liu, Xin, Scott, John W., Oakhill, Jonathan S., Galic, Sandra, Shi, Yanchuan, Moreno-Asso, Alba, Smith, Cassandra, Loudovaris, Thomas, Levinger, Itamar, Eizirik, Decio L., Laybutt, D. Ross, Herzog, Herbert, Thomas, Helen E. and Loh, Kim. (2022). Neuropeptide Y1 receptor antagonism protects β-cells and improves glycemic control in type 2 diabetes. Molecular Metabolism. 55(1), p. Article 101413. https://doi.org/10.1016/j.molmet.2021.101413
An AMPKa2-specific phospho-switch controls lysosomal targeting for activation
Morrison, Kaitlin R., Smiles, William J., Ling, Naomi X. Y., Hoque, Ashfaqul, Shea, Gabrielle, Ngoei, Kevin R. W., Yu, Dingyi, Murray-Segal, Lisa, Scott, John W., Galic, Sandra, Kemp, Bruce E., Petersen, Janni and Oakhill, Jonathan S.. (2022). An AMPKa2-specific phospho-switch controls lysosomal targeting for activation. Cell Reports. 38(7), p. Article 110365. https://doi.org/10.1016/j.celrep.2022.110365
Personalized phosphoproteomics identifies functional signaling
Needham, Elise J., Hingst, Janne R., Parker, Benjamin L., Morrison, Kaitlin R., Yang, Guang, Onslev, Johan, Kristensen, Jonas M., Højlund, Kurt, Ling, Naomi, Oakhill, Jonathan X. Y., Richter, Erik A., Kiens, Bente, Petersen, Janni, Pehmøller, Christian, James, David E., Wojtaszewski, Jørgen F. P. and Humphrey, Sean J.. (2022). Personalized phosphoproteomics identifies functional signaling. Nature Biotechnology. 40(4), pp. 576-584. https://doi.org/10.1038/s41587-021-01099-9
A novel small molecule inhibitor of human Drp1
Rosdah, Ayeshah A., Abbott, Belinda M., Langendorf, Christopher G., Deng, Yali, Truong, Jia Q., Waddell, Helen M. M., Ling, Naomi X. Y., Smiles, William J., Delbridge, Lea M. D., Liu, Guei-Sheung, Oakhill, Jonathan S., Lim, Shiang Y. and Holien, Jessica K.. (2022). A novel small molecule inhibitor of human Drp1. Scientific Reports. 12(1), p. Article 21531. https://doi.org/10.1038/s41598-022-25464-z
Blocking AMPK β1 myristoylation enhances AMPK activity and protects mice from high-fat diet-induced obesity and hepatic steatosis
Neopane, Katyayanee, Kozlov, Natalie, Negoita, Florentina, Murray-Segal, Lisa, Brink, Robert, Hoque, Ashfaqul, Ovens, Ashley J., Tjin, Gavin, McAloon, Luke M., Yu, Dingyi, Ling, Naomi X. Y., Sanders, Matthew J., Oakhill, Jonathan S., Scott, John W., Steinberg, Gregory R., Loh, Kim, Kemp, Bruce E., Sakamoto, Kei and Galic, Sandra. (2022). Blocking AMPK β1 myristoylation enhances AMPK activity and protects mice from high-fat diet-induced obesity and hepatic steatosis. Cell Reports. 41(12), pp. 1-16. https://doi.org/10.1016/j.celrep.2022.111862
Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator
Ovens, Ashley J., Gee, Yi Sing, Ling, Naomi X. Y., Yu, Dingyi, Hardee, Justin P., Chung, Jin D., Ngoei, Kevin R. W., Waters, Nicholas J., Hoffman, Nolan J., Scott, John W., Loh, Kim, Spengler, Katrin, Heller, Regine, Parker, Michael W., Lynch, Gordon S., Huang, Fei, Galic, Sandra, Kemp, Bruce E., Baell, Jonathan B., ... Langendorf, Christopher G.. (2022). Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator. Biochemical Journal. 479(11), pp. 1181-1204. https://doi.org/10.1042/BCJ20220067
Calcium/calmodulin-dependent protein kinase kinase 2 regulates hepatic fuel metabolism
Stork, Britanny A., Dean, Adam, Ortiz, Andrea R., Saha, Pradip, Putluri, Nagireddy, Planas-Silva, Maricarmen D., Mahmud, Iqbal, Rajapakshe, Kimal, Coarfa, Cristian, Knapp, Stefan, Lorenzi, Philip L., Kemp, Bruce E., Turk, Benjamin E., Scott, John W., Means, Anthony R. and York, Brian. (2022). Calcium/calmodulin-dependent protein kinase kinase 2 regulates hepatic fuel metabolism. Molecular Metabolism. 62, p. Article 101513. https://doi.org/10.1016/j.molmet.2022.101513
Inhibition of ATP-citrate lyase improves NASH, liver fibrosis, and dyslipidemia
Morrow, Marisa R., Batchuluun, Battsetseg, Wu, Jianhan, Ahmadi, Elham, Leroux, Julie M., Mohammadi-Shemirani, Pedrum, Desjardins, Eric M., Wang, Zhichao, Tsakiridis, Evangelia E., Lavoie, Declan C. T., Reihani, Amir, Smith, Brennan K., Kwiecien, Jacek M., Lally, James S. V., Nero, Tracy L., Parker, Michael W., Ask, Kjetil, Scott, John W., Jiang, Lei, ... Steinberg, Gregory R.. (2022). Inhibition of ATP-citrate lyase improves NASH, liver fibrosis, and dyslipidemia. Cell Metabolism. 34(6), pp. 919-936. https://doi.org/10.1016/j.cmet.2022.05.004
Genetic impairment of succinate metabolism disrupts bioenergetic sensing in adrenal neuroendocrine cancer
Gupta, Priyanka, Strange, Keehn, Telange, Rahul, Guo, Ailan, Hatch, Heather, Sobh, Amin, Elie, Jonathan, Carter, Angela M., Totenhagen, John, Tan, Chunfeng, Sonawane, Yogesh A., Neuzil, Jiri, Natarajan, Amarnath, Ovens, Ashley J., Oakhill, Jonathan S., Wiederhold, Thorsten, Pacak, Karel, Ghayee, Hans K., Meijer, Laurent, ... Bibb, James A.. (2022). Genetic impairment of succinate metabolism disrupts bioenergetic sensing in adrenal neuroendocrine cancer. Cell Reports. 40(7), p. Article 111218. https://doi.org/10.1016/j.celrep.2022.111218
Phosphoproteomics of three exercise modalities identifies canonical signaling and C180RF25 as an AMPK substrate regulating skeletal muscle function
Blazev, Ronnie, Carl, Christian S., Ng, Yaan-Kit, Molendijk, Jeffrey, Voldstedlund, Christian T., Zhao, Yuanyuan, Xiao, Di, Kueh, Andrew J., Miotto, Paula M., Haynes, Vanessa R., Hardee, Justin P., Chung, Jin D., MacNamara, James W., Qian, Hongwei, Gregorevic, Paul, Oakhill, Jonathan S., Herold, Marco J., Jensen, Thomas E., Lisowski, Leszek, ... Parker, Benjamin L.. (2022). Phosphoproteomics of three exercise modalities identifies canonical signaling and C180RF25 as an AMPK substrate regulating skeletal muscle function. Cell Metabolism. 34, pp. 1561-1577.e9. https://doi.org/10.1016/j.cmet.2022.07.003
Regulation of pancreatic β-cell function by the NPY system
Yang, Chieh-Hsin, Onda, Danise-Ann, Oakhill, Jonathan S., Scott, John W., Galic, Sandra and Loh, Kim. (2021). Regulation of pancreatic β-cell function by the NPY system. Endocrinology. 162(8), pp. 1-8. https://doi.org/10.1210/endocr/bqab070
Post-translational modifications of the energy guardian AMP-activated protein kinase
Ovens, Ashley J., Scott, John W., Langendorf, Christopher G., Kemp, Bruce E., Oakhill, Jonathan S. and Smiles, William J.. (2021). Post-translational modifications of the energy guardian AMP-activated protein kinase. International Journal of Molecular Sciences. 22(3), p. Article 1229. https://doi.org/10.3390/ijms22031229
Molecular mechanisms underlying the beneficial effects of exercise on brain function and neurological disorders
Nay, Kévin, Smiles, William J., Kaiser, Jacqueline, McAloon, Luke M., Loh, Kim, Galic, Sandra, Oakhill, Jonathan S., Gundlach, Andrew L. and Scott, John W.. (2021). Molecular mechanisms underlying the beneficial effects of exercise on brain function and neurological disorders. International Journal of Molecular Sciences. 22, p. Article 4052. https://doi.org/10.3390/ijms22084052
Hinge binder scaffold hopping identifies potent calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) inhibitor chemotypes
Eduful, Benjamin J., O'Byrne, Sean N., Temme, Louisa, Asquith, Christopher R. M., Liang, Yi, Picado, Alfredo, Pilotte, Joseph R., Hossain, Mohammad Anwar, Wells, Carrow I., Zuercher, William J., Catta-Preta, Carolina M.C, Ramos, Priscila, de S. Santiago, André, Counago, Rafael M., Langendorf, Christopher G., Nay, Kevin, Oakhill, Jonathan S., Pulliam, Thomas L., Lin, Chenchu, ... Drewry, David H.. (2021). Hinge binder scaffold hopping identifies potent calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) inhibitor chemotypes. Journal of Medicinal Chemistry. 64(15), pp. 10849-10877. https://doi.org/10.1021/acs.jmedchem.0c02274
Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965
Ahwazi, Danial, Neopane, Katyayanee, Markby, Greg, Kopietz, Franziska, Ovens, Ashley, Dall, Morten, Hassing, Anna, Graesle, Pamina, Alshuweishi, Yazeed, Treebak, Jonas, Salt, Ian, Goransson, Olga, Zeqiraj, Elton, Scott, John Walter and Sakamoto, Kei. (2021). Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965. Biochemical Journal. 478(15), pp. 2977-2997. https://doi.org/10.1042/BCJ20210284
Compound- and fiber type-selective requirement of AMPKγ3 for insulin-independent glucose uptake in skeletal muscle
Rhein, Philipp, Desjardins, Eric M., Rong, Ping, Ahwazi, Danial, Bonhoure, Nicolas, Stolte, Jens, Santos, Matthieu D., Ovens, Ashley J., Ehrlich, Amy M., Sanchez Garcia, José L., Ouyang, Qian, Yabut, Julian M., Kjolby, Mads, Membrez, Mathieu, Jessen, Niels, Oakhill, Jonathan S., Treebak, Jonas T., Maire, Pascal, Scott, John W., ... Sakamoto, Kei. (2021). Compound- and fiber type-selective requirement of AMPKγ3 for insulin-independent glucose uptake in skeletal muscle. Molecular Metabolism. 51, p. Article: 101228. https://doi.org/10.1016/j.molmet.2021.101228
New perspectives on the role of Drp1 isoforms in regulating mitochondrial pathophysiology
Rosdah, Ayeshah A., Smiles, William J., Oakhill, Jonathan S., Scott, John W., Langendorf, Christopher G., Delbridge, Lea M. D., Holien, Jessica K. and Lim, Shiang Y.. (2020). New perspectives on the role of Drp1 isoforms in regulating mitochondrial pathophysiology. Pharmacology and Therapeutics. 213, p. Article 107594. https://doi.org/10.1016/j.pharmthera.2020.107594
Protein kinase a negatively regulates VEGF-induced AMPK activation by phosphorylating CaMKK2 at serine 495
Spengler, Katrin, Zibrova, Darya, Woods, Angela, Langendorf, Christopher G., Scott, John W., Carling, David and Heller, Regine. (2020). Protein kinase a negatively regulates VEGF-induced AMPK activation by phosphorylating CaMKK2 at serine 495. Biochemical Journal. 477(17), pp. 3453-3469. https://doi.org/10.1042/BCJ20200555
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
Xy Ling, Naomi, Langendorf, Christopher G., Hoque, Ashfaqul, Galic, Sandra, Loh, Kim, Kemp, Bruce E., Gundlach, Andrew L., Oakhill, Jonathan S. and Scott, John W.. (2020). 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. Bipolar Disorders. 22(8), pp. 841-848. https://doi.org/10.1111/bdi.12901
CaMKK2 is inactivated by cAMP-PKA signaling and 14-3-3 adaptor proteins
Langendorf, Christopher G., O'Brien, Matthew T., Ngoei, Kevin R. W., McAloon, Luke M., Dhagat, Urmi, Hoque, Ashfaqul, Ling, Naomi X. Y., Dite, Toby A., Galic, Sandra, Loh, Kim, Parker, Michael W., Oakhill, Jonathan S., Kemp, Bruce E. and Scott, John W.. (2020). CaMKK2 is inactivated by cAMP-PKA signaling and 14-3-3 adaptor proteins. Journal of Biological Chemistry. 295(48), pp. 16239-16250. https://doi.org/10.1074/jbc.RA120.013756
DNA-dependent protein kinase regulates lysosomal AMP-dependent protein kinase activation and autophagy
Puustinen, Pietri, Keldsbo, Anne, Corcelle-Termeau, Elisabeth, Ngoei, Kevin, Sønder, Stine L., Farkas, Thomas, Kaae Andersen, Klaus, Oakhill, Jon S. and Jäättelä, Marja. (2020). DNA-dependent protein kinase regulates lysosomal AMP-dependent protein kinase activation and autophagy. Autophagy. 16(10), pp. 1871-1888. https://doi.org/10.1080/15548627.2019.1710430
The myokine meteorin-like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKa2
Lee, Jung Ok, Byun, Won Seok, Kang, Min Ju, Han, Jeong Ah, Moon, Jiyoung, Shin, Min-Jeong, Lee, Ho Jun, Chung, Ji Hyung, Lee, Jin-Seok, Son, Chang-Gue, Song, Kwon-Ho, Kim, Tae Woo, Lee, Eun-Soo, Kim, Hong Min, Chung, Choon Hee, Ngoei, Kevin R. W., Ling, Naomi X. Y., Oakhill, Jonathan S., Galic, Sandra, ... Kim, Hyeon Soo. (2020). The myokine meteorin-like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKa2. The FEBS Journal. 287(10), pp. 2087-2104. https://doi.org/10.1111/FEBS.15301
The eEF2 kinase-induced STAT3 inactivation inhibits lung cancer cell proliferation by phosphorylation of PKM2
Xiao, Min, Xie, Jianling, Wu, Yu, Wang, Genzhu, Qi, Xin, Liu, Zailiang, Wang, Yuying, Wang, Xuemin, Hoque, Ashfaqul, Oakhill, Jon, Proud, Christopher G. and Li, Jing. (2020). The eEF2 kinase-induced STAT3 inactivation inhibits lung cancer cell proliferation by phosphorylation of PKM2. Cell Communication and Signaling. 18(1), p. 25.
mTORC1 directly inhibits AMPK to promote cell proliferation under nutrient stress
Ling, Naomi X. Y., Kaczmarek, Adrian, Hoque, Ashfaqul, Davie, Elizabeth, Ngoei, Kevin R. W., Morrison, Kaitlin R., Smiles, William J., Forte, Gabriella M., Wang, Tingting, Lie, Shervi, Dite, Toby A., Langendorf, Christopher G., Scott, John W., Oakhill, Jonathan S. and Petersen, Janni. (2020). mTORC1 directly inhibits AMPK to promote cell proliferation under nutrient stress. Nature Metabolism. 2, pp. 41-49. https://doi.org/10.1038/s42255-019-0157-1
In depth analysis of kinase cross screening data to identify CaMKK2 inhibitory scaffolds
O’Byrne, Sean N., Scott, John W., Pilotte, Joseph R., Santiago, André da S., Langendorf, Christopher G., Oakhill, Jonathan S., Eduful, Benjamin J., Couñago, Rafael M., Wells, Carrow I., Zuercher, William J., Willson, Timothy M. and Drewry, David H.. (2020). In depth analysis of kinase cross screening data to identify CaMKK2 inhibitory scaffolds. Molecules. 25(2), pp. 1-19. https://doi.org/10.3390/molecules25020325
Genetic loss of AMPK-glycogen binding destabilizes AMPK and disrupts metabolism
Hoffman, Nolan J., Whitfield, Jamie, Janzen, Natalie R., Belhaj, Mehdi R., Galic, Sandra, Murray-Segal, Lisa, Smiles, William J., Ling, Naomi X. Y., Dite, Toby A., Scott, John W., Oakhill, Jonathan S., Brink, Robert, Kemp, Bruce E. and Hawley, John A.. (2020). Genetic loss of AMPK-glycogen binding destabilizes AMPK and disrupts metabolism. Molecular Metabolism. 41, pp. 1-13. https://doi.org/10.1016/j.molmet.2020.101048
Long-chain fatty acyl-CoA esters regulate metabolism via allosteric control of AMPK β1 isoforms
Pinkosky, Stephen L., Scott, John W., Desjardins, Eric M., Smith, Brennan K., Day, Emily A., Ford, Rebecca J., Langendorf, Christopher G., Ling, Naomi X. Y., Nero, Tracy L., Loh, Kim, Galic, Sandra, Hoque, Ashfaqul, Smiles, William J., Ngoei, Kevin R. W., Parker, Michael W., Yan, Yan, Melcher, Karsten, Kemp, Bruce E., Oakhill, Jonathan S. and Steinberg, Gregory R.. (2020). Long-chain fatty acyl-CoA esters regulate metabolism via allosteric control of AMPK β1 isoforms. Nature Metabolism. 2(9), pp. 873-881. https://doi.org/10.1038/s42255-020-0245-2
Allosteric regulation of AMP-activated protein kinase by adenylate nucleotides and small-molecule drugs
de Souza Almeida Matos, Ana Laura, Oakhill, Jonathan S., Moreira, José, Loh, Kim, Galic, Sandra and Scott, John W.. (2019). Allosteric regulation of AMP-activated protein kinase by adenylate nucleotides and small-molecule drugs. Biochemical Society Transactions. 47(2), pp. 733 - 741. https://doi.org/10.1042/BST20180625
AMP-activated protein kinase complexes containing the beta2 regulatory subunit are up-regulated during and contribute to adipogenesis
Katwan, Omar J., Alghamdi, Fatmah, Almabrouk, Tarek A., Mancini, Sarah J., Kennedy, Simon, Oakhill, Jonathan S., Scott, John W. and Salt, Ian P.. (2019). AMP-activated protein kinase complexes containing the beta2 regulatory subunit are up-regulated during and contribute to adipogenesis. Biochemical Journal. 476(12), pp. 1725 - 1740. https://doi.org/10.1042/BCJ20180714
Inhibition of adenosine monophosphate-activated protein kinase-3-hydroxy-3-methylglutaryl coenzyme a reductase signaling leads to hypercholesterolemia and promotes hepatic steatosis and insulin resistance
Loh, Kim, Tam, Shanna, Murray-Segal, Lisa, Huynh, Kevin, Meikle, Peter J., Scott, John W., van Denderen, Bryce J., Chen, Zhiping, Steel, Rohan, LeBlond, Nicholas D., Burkovsky, Leah A., O'Dwyer, Conor, Nunes, Julia R. C., Steinberg, Gregory R., Fullerton, Morgan D., Galic, Sandra and Kemp, Bruce E.. (2019). Inhibition of adenosine monophosphate-activated protein kinase-3-hydroxy-3-methylglutaryl coenzyme a reductase signaling leads to hypercholesterolemia and promotes hepatic steatosis and insulin resistance. Hepatology Communications. 3(1), pp. 84 - 98. https://doi.org/10.1002/hep4.1279
Transient expression of AMPK heterotrimer complexes in mammalian cells
Jon Oakhill, John Scott and Toby A. Dite. (2018). Transient expression of AMPK heterotrimer complexes in mammalian cells. In AMPK pp. 159-169 Humana Press, Inc.. https://doi.org/10.1007/978-1-4939-7598-3_10
Autophagy induced during apoptosis degrades mitochondria and inhibits type I interferon secretion
Lindqvist, Lisa M., Frank, Daniel, McArthur, Kate, Dite, Toby A., Lazarou, Michael, Oakhill, Jon, Kile, Benjamin T. and Vaux, David L.. (2018). Autophagy induced during apoptosis degrades mitochondria and inhibits type I interferon secretion. Cell Death and Differentiation. 25(4), pp. 782 - 794. https://doi.org/10.1038/s41418-017-0017-z
Structural determinants for small-molecule activation of skeletal muscle AMPK α2β2γ1 by the glucose importagog sc4
Ngoei, Kevin R.W., Langendorf, Christopher G., Ling, Naomi, Hoque, Ashfaqul, Johnson, Swapna, Camerino, Michelle C., Walker, Scott R., Bozikis, Ylva E., Dite, Toby A., Ovens, Ashley J., Smiles, William, Jacobs, Roxane, Huang, He, Parker, Michael W., Scott, John W., Rider, Mark H., Foitzik, Richard C., Kemp, Bruce, Baell, Jonathan B. and Oakhill, Jonathan S.. (2018). Structural determinants for small-molecule activation of skeletal muscle AMPK α2β2γ1 by the glucose importagog sc4. Cell Chemical Biology. 25(6), pp. 728 - 737. https://doi.org/10.1016/j.chembiol.2018.03.008
Mitochondrial fission protein Drp1 inhibition promotes cardiac mesodermal differentiation of human pluripotent stem cells
Hoque, Ashfaqul, Sivakumaran, Priyadharshini, Bond, Simon T., Ling, Naomi, Kong, Anne M., Scott, John W., Bandara, Nadeeka, Hernandez, Damian, Liu, Guei-Sheung, Wong, Raymond, Ryan, Michael T., Hausenloy, Derek, Kemp, Bruce, Oakhill, Jonathan S., Drew, Brian, Pebay, Alice and Lim, Shiang Y.. (2018). Mitochondrial fission protein Drp1 inhibition promotes cardiac mesodermal differentiation of human pluripotent stem cells. Cell Death Discovery. 4(39), pp. 1 - 13. https://doi.org/10.1038/s41420-018-0042-9
AMP-activated protein kinase selectively inhibited by the type II inhibitor SBI-0206965
Dite, Toby A., Langendorf, Christopher, Hoque, Ashfaqul, Galic, Sandra, Rebello, Richard J., Ovens, Ashley J., Lindqvist, Lisa M., Ngoei, Kevin R.W., Ling, Naomi, Furic, Luc, Kemp, Bruce, Scott, John W. and Oakhill, Jonathan S.. (2018). AMP-activated protein kinase selectively inhibited by the type II inhibitor SBI-0206965. Journal of Biological Chemistry. 293(23), pp. 8874 - 8885. https://doi.org/10.1074/jbc.RA118.003547
1,2,6-thiadiazinones as novel narrow spectrum calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) inhibitors
Asquith, Christopher R.M., Godoi, Paulo H., Counago, Rafael M., Laitinen, Tuomo, Scott, John W., Langendorf, Christopher G., Oakhill, Jonathan S., Drewry, David H., Zuercher, William J., Koutentis, Panayiotis A., Willson, Timothy M. and Kalogirou, Andreas S.. (2018). 1,2,6-thiadiazinones as novel narrow spectrum calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) inhibitors. Molecules. 23(5), pp. 1 - 23. https://doi.org/10.3390/molecules23051221
Impact of genetic variation on human CaMKK2 regulation by Ca2+ -calmodulin and multisite phosphorylation
O'Brien, Matthew, Oakhill, Jonathan S., Ling, Naomi, Langendorf, Christopher G., Hoque, Ashfaqul, Dite, Toby A., Means, Anthony R., Kemp, Bruce and Scott, John W.. (2017). Impact of genetic variation on human CaMKK2 regulation by Ca2+ -calmodulin and multisite phosphorylation. Scientific Reports. 7, pp. 1 - 11. https://doi.org/10.1038/srep43264
The sweet side of AMPK signaling: Regulation of GFAT1
Scott, John W. and Oakhill, Jonathan S.. (2017). The sweet side of AMPK signaling: Regulation of GFAT1. Biochemical Journal. 474(7), pp. 1289 - 1292. https://doi.org/10.1042/BCJ20170006
The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs
Dite, Toby A., Ling, Naomi, Scott, John W., Hoque, Ashfaqul, Galic, Sandra, Parker, Benjamin L., Ngoei, Kevin R.W., Langendorf, Christopher G., O'Brien, Matthew, Kundu, Mondira, Viollet, Benoit, Steinberg, Gregory R., Sakamoto, Kei, Kemp, Bruce and Oakhill, Jonathan S.. (2017). The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs. Nature Communications. 8(571), pp. 1 - 14. https://doi.org/10.1038/s41467-017-00628-y
Fake inhibitors: AMPK activation trumps inhibition
Langendorf, Christopher G., Scott, John W. and Kemp, Bruce E.. (2017). Fake inhibitors: AMPK activation trumps inhibition. Cell Chemical Biology. 24(7), pp. 775 - 777. https://doi.org/10.1016/j.chembiol.2017.07.005
Cyclin-dependent kinase-mediated phosphorylation of breast cancer metastasis suppressor 1 (BRMS1) affects cell migration
Roesley, Siti Nur Ain, Suryadinata, Randy, Morrish, Emma, Tan, Anthonius Ricardo, Issa, Samah M. A., Oakhill, Jon, Bernard, Ora, Welch, Danny R. and Sarcevic, Boris. (2016). Cyclin-dependent kinase-mediated phosphorylation of breast cancer metastasis suppressor 1 (BRMS1) affects cell migration. Cell Cycle. 15(1), pp. 137 - 151. https://doi.org/10.1080/15384101.2015.1121328
Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding
Langendorf, Christopher G., Ngoei, Kevin R. W., Scott, John W., Ling, Naomi X. Y., Issa, Sam M. A., Gorman, Michael A., Parker, Michael W., Sakamoto, Kei, Oakhill, Jonathan S. and Kemp, Bruce Ernest. (2016). Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding. Nature Communications. 7, pp. 1 - 8. https://doi.org/10.1038/ncomms10912
The social supply of cannabis among young people in Australia
Lenton, Simon, Grigg, Jodie, Scott, John, Barratt, Monica and Eleftheriadis, Dina. (2015). The social supply of cannabis among young people in Australia. Trends and Issues in Crime and Criminal Justice. (503), pp. 1-6.
Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity
Ford, Rebecca, Fullerton, Morgan, Pinkosky, Stephen, Day, Emily, Scott, John, Oakhill, Jonathan, Bujak, Adam, Smith, Brennan, Crane, Justin, Blumer, Regje, Marcinko, Katarina, Kemp, Bruce, Gerstein, Hertzel and Steinberg, Gregory. (2015). Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity. Biochemical Journal. 468(1), pp. 125 - 132. https://doi.org/10.1042/BJ20150125
Inhibition of AMP-activated protein kinase at the allosteric drug-binding site promotes islet insulin release
Scott, John, Galic, Sandra, Graham, Kate, Foitzik, Richard, Ling, Naomi, Dite, Toby, Issa, Samah, Langendorf, Chris, Weng, Qing, Thomas, Helen, Kay, Thomas, Birnberg, Neal, Steinberg, Gregory, Kemp, Bruce and Oakhill, Jonathan. (2015). Inhibition of AMP-activated protein kinase at the allosteric drug-binding site promotes islet insulin release. Chemistry and Biology. 22(6), pp. 705 - 711. https://doi.org/10.1016/j.chembiol.2015.05.011
Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder
Scott, John, Park, Elizabeth, Rodriguiz, Ramona, Oakhill, Jonathan, Issa, Samah, O'Brien, Matthew, Dite, Toby, Langendorf, Christopher, Wetsel, William, Means, Anthony and Kemp, Bruce. (2015). Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder. Scientific Reports. 5, pp. 1 - 10. https://doi.org/10.1038/srep14436
SnRK1 from Arabidopsis thaliana is an atypical AMPK
Emanuelle, Shane, Hossain, Mohammed Iqbal, Moller, Isabel E., Pedersen, Henriette L., van de Meene, Allison M. L., Doblin, Monika S., Koay, Ann, Oakhill, Jonathan S., Scott, John W., Willats, William G. T., Kemp, Bruce Ernest, Bacic, Antony, Gooley, Paul R. and Stapleton, David I.. (2015). SnRK1 from Arabidopsis thaliana is an atypical AMPK. Plant Journal. 82(2), pp. 183 - 192. https://doi.org/10.1111/tpj.12813
Mutant TDP-43 deregulates AMPK activation by PP2A in ALS models
Perera, Nirma, Sheean, Rebecca, Scott, John, Kemp, Bruce, Horne, Malcolm and Turner, Bradley. (2014). Mutant TDP-43 deregulates AMPK activation by PP2A in ALS models. PLoS One (online). 9(3), pp. 1 - 11. https://doi.org/10.1371/journal.pone.0090449
ATP sensitive bi-quinoline activator of the AMP-activated protein kinase
Scott, John, Oakhill, Jonathan, Ling, Naomi, Langendorf, Christopher, Foitzik, Richard, Kemp, Bruce and Issinger, Olaf-Georg. (2014). ATP sensitive bi-quinoline activator of the AMP-activated protein kinase. Biochemical and Biophysical Research Communications. 443(2), pp. 435 - 440. https://doi.org/10.1016/j.bbrc.2013.11.130
Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling
Scott, John, Ling, Naomi, Issa, Samah, Dite, Toby, O'Brien, Matthew, Chen, Zhi-Ping, Galic, Sandra, Langendorf, Christopher, Steinberg, Gregory, Kemp, Bruce and Oakhill, Jonathan. (2014). Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling. Chemistry and Biology. 21(5), pp. 619 - 627. https://doi.org/10.1016/j.chembiol.2014.03.006
Differences between first episode schizophrenia and schizoaffective disorder
Cotton, Sue, Lambert, M, Schimmelmann, B, Mackinnon, Andrew, Gleeson, John, Berk, Michael, Hides, L, Chanen, Andrew, Scott, J and Schottle, D. (2013). Differences between first episode schizophrenia and schizoaffective disorder. Schizophrenia Research. https://doi.org/10.1016/j.schres.2013.02.036
Ca 2+/calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation
Green, Michelle, Scott, John, Steel, Rohan, Oakhill, Jonathan, Kemp, Bruce and Means, Anthony. (2011). Ca 2+/calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation. Journal of Biological Chemistry. 286(32), pp. 28066 - 28079. https://doi.org/10.1074/jbc.M111.251504
AMPK is a direct adenylate charge-regulated protein kinase
Oakhill, Jonathan S., Steel, Rohan, Chen, Zhi-Ping, Scott, John W., Ling, Naomi, Tam, Shanna and Kemp, Bruce Ernest. (2011). AMPK is a direct adenylate charge-regulated protein kinase. Science. 332(6036), pp. 1433 - 1435. https://doi.org/10.1126/science.1200094