title: Histone H4 histidine kinase displays the expression pattern of a liver oncodevelopmental marker.
abstract: Protein phosphorylation is a vital process in the regulation of mammalian cell division and the protein kinases that catalyze the phosphorylation of proteins on serine, threonine and tyrosine residues have been well characterized. In contrast, little is known about the kinases involved in protein histidine phosphorylation, which have been described in various mammalian cells that are highly proliferative. Histone H4 histidine kinase (HHK) activity is highly active in regenerating rat liver. Using a novel and specific assay, we demonstrate that it is active in human fetal liver, essentially absent in adult liver and highly expressed in liver tumours. 'Normal' liver surrounding the HCC contains low to undetectable levels of HHK. In a rodent model of chronic liver injury that leads to HCC, its activity is induced. Two lines of evidence suggest that liver progenitor (oval) cells, which populate the liver at early stages following induction of liver damage are responsible for the increased activity. Purified oval cells, as well as cell lines established from primary cultures of oval cells express high levels of HHK. We propose that the pattern of expression of histone H4 histidine kinase activity justifies its classification as an oncodevelopmental marker and suggest it may be useful as a diagnostic marker for hepatocellular carcinoma as well for identifying preneoplastic lesions.
authors.affiliation: Biochemistry and Molecular Biology, School of Biomedical and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia.
authors.forename: Eiling
authors.initials: E
authors.lastname: Tan
authors.forename: Paul G
authors.initials: PG
authors.lastname: Besant
authors.forename: Xin Lin
authors.initials: XL
authors.lastname: Zu
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Turck
authors.forename: Marie A
authors.initials: MA
authors.lastname: Bogoyevitch
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
authors.forename: Paul V
authors.initials: PV
authors.lastname: Attwood
authors.forename: George C
authors.initials: GC
authors.lastname: Yeoh
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D006498:Hepatectomy; D022781:Hepatocytes / Q000201:enzymology*; D000071677:Histidine Kinase; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008099:Liver / Q000196:embryology / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018809:Proliferating Cell Nuclear Antigen; D011494:Protein Kinases; D000071677:Histidine Kinase