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A new protein kinase cascade

Nature Reviews Molecular Cell Biology volume 15, page 223 (2014)Cite this article

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The concept of a kinase cascade is now familiar, but in 1978 only one of these, the protein kinase A (PKA)–phosphorylase kinase cascade ... was known.

In 1978, when I was just setting up my own laboratory, a short paper from David Gibson's group at the Indiana University School of Medicine, Indianapolis, USA, (Ingebritsen et al.) suggested that a protein kinase that inactivated the cholesterol biosynthetic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase was itself activated by phosphorylation and was therefore part of a kinase cascade. The concept of a kinase cascade is now familiar, but in 1978 only one of these, the protein kinase A (PKA)–phosphorylase kinase cascade, which was discovered by Ed Krebs, was known. More remarkable still, fewer than ten protein kinases (including the kinase for HMG-CoA reductase ('reductase kinase') and an apparently unrelated kinase for acetyl-CoA carboxylase) had been defined and only then in terms of their enzyme activity (the first kinase domain sequence, which was of PKA, was not determined until 1981).

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References

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  1. Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK

    D. Grahame Hardie

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  1. D. Grahame Hardie
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Correspondence to D. Grahame Hardie.

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Hardie, D. A new protein kinase cascade. Nat Rev Mol Cell Biol 15, 223 (2014). https://doi.org/10.1038/nrm3771

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