Protein ubiquitylation and protein phosphorylation are the two major mechanisms that regulate the functions of proteins in eukaryotic cells. However, these different posttranslational modifications do not operate independently of one another, but are frequently interlinked to enable biological processes to be controlled in a more complex and sophisticated manner. Studying how protein phosphorylation events control the ubiquitin system and how ubiquitylation regulates protein phosphorylation has become a focal point of the study of cell regulation and human disease. Cloning of human Brain Specific Kinase 2 (BRSK2) was first described by Miura et al. (1998). BRSK2 is a member of the subfamily of protein kinases that include the AMP-activated protein kinase (AMPK) and, like AMPK itself, is activated by the tumour suppressor kinase LKB1 (Lizcano et al., 2004). As implied by its name BRSK2 is expressed in the brain where it plays an essential role in controlling neuronal cell polarisation. BRSK2 contains a ubiquitin-like domain adjacent to the kinase catalytic domain (Al-Hakim et al., 2008).
Al-Hakim AK, Zagorska A, Chapman L, Deak M, Peggie M, Alessi DR (2008) Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains. Biochem J 411, 249-60.
Hastie CJ, McLauchlan HJ, Cohen P (2006) Assay of protein kinases using radiolabeled ATP: a protocol. Nat Protoc 1, 968-71.
Miura K, Masuzaki H, Ishimaru T, Niikawa N, Jinno Y (1998) A HhaI/BstUI polymorphism in a novel gene at human chromosome 11p15.5. J Hum Genet 90, 283-4.
Lizcano JM, Goransson O, et al. (2004) LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J 23, 833-43.
Background kindly written by:
Sir Philip Cohen FRS, FRSE
University of Dundee
Director of the Medical Research Council Protein Phosphorylation Unit (1990-2012)
Director of the Scottish Institute for Cell Signalling incorporating the Protein Ubiquitylation Unit (2008-2012)
Co-Director of the Division of Signal Transduction Therapy (1998-2012)
Deputy Director of the Division of Signal Transduction Therapy (from July 2012)
Professor Cohen's research group is studying the interplay between protein phosphorylation and protein ubiquitylation in the regulation of innate immunity.