Regulation of the AMPK-related protein kinases by ubiquitination.
How can a constitutively active 'master' kinase with numerous downstream targets preferentially phosphorylate one or more of these without influencing all simultaneously? How might such a system be switched off? The characterization of the role of deubiquitination in regulating the phosphorylation and activation of AMPK (AMP-activated protein kinase)-related kinases by LKB1 suggests a novel and interesting mechanism for conferring signal transduction specificity and control at the kinase substrate level. In this issue of the Biochemical Journal, Al-Hakim et al. show that the AMPK-related kinases NUAK1 (AMPK-related kinase 5) and MARK4 (microtubule-affinity-regulating kinase 4) are polyubiquitinated in vivo and that they serve as substrates of the deubiquitinating enzyme USP9X; furthermore, the first evidence is provided for regulation of AMPK-related kinase family members mediated via unusual Lys(29)/Lys(33) polyubiquitin chains, rather than the more common Lys(48)/Lys(63) linkages.
Thomson
David M
DM
Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
Hansen
Marc D H
MD
Winder
William W
WW
D055372:AMP-Activated Protein Kinases; D006801:Humans; D009097:Multienzyme Complexes / Q000737:chemistry*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism*; D012680:Sensitivity and Specificity; D054875:Ubiquitination
D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases