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Link to original content: https://pubmed.ncbi.nlm.nih.gov/14614828
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. 2003 Nov 11;13(22):2004-8.
doi: 10.1016/j.cub.2003.10.031.

LKB1 is the upstream kinase in the AMP-activated protein kinase cascade

Angela Woods  1 , Stephen R Johnstone, Kristina Dickerson, Fiona C Leiper, Lee G D Fryer, Dietbert Neumann, Uwe Schlattner, Theo Wallimann, Marian Carlson, David Carling
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Free article

LKB1 is the upstream kinase in the AMP-activated protein kinase cascade

Angela Woods et al. Curr Biol. .
Free article

Abstract

Inactivating mutations in the protein kinase LKB1 lead to a dominantly inherited cancer in humans termed Peutz-Jeghers syndrome. The role of LKB1 is unclear, and only one target for LKB1 has been identified in vivo [3]. AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that plays a pivotal role in energy homeostasis. AMPK may have a role in protecting the body from metabolic diseases including type 2 diabetes, obesity, and cardiac hypertrophy. We previously reported the identification of three protein kinases (Elm1, Pak1, and Tos3 [9]) that lie upstream of Snf1, the yeast homologue of AMPK. LKB1 shares sequence similarity with Elm1, Pak1, and Tos3, and we demonstrated that LKB1 phosphorylates AMPK on the activation loop threonine (Thr172) within the catalytic subunit and activates AMPK in vitro [9]. Here, we have investigated whether LKB1 corresponds to the major AMPKK activity present in cell extracts. AMPKK purified from rat liver corresponds to LKB1, and blocking LKB1 activity in cells abolishes AMPK activation in response to different stimuli. These results identify a link between two protein kinases, previously thought to lie in unrelated, distinct pathways, that are associated with human diseases.

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Comment in

  • A new protein kinase cascade.
    Hardie DG. Hardie DG. Nat Rev Mol Cell Biol. 2014 Apr;15(4):223. doi: 10.1038/nrm3771. Epub 2014 Mar 12. Nat Rev Mol Cell Biol. 2014. PMID: 24622616 No abstract available.

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