title: Activation of Jun kinase is an early event in hepatic regeneration.
abstract: Compensatory hepatic regeneration after partial hepatectomy (PH) is dependent upon the extent of resection. This study analyzes the regulation of the AP-1 transcription factor c-Jun during hepatic regeneration. There is a progressive increase in c-jun mRNA levels after sham operation, one-third PH, and two-thirds PH. A concomitant increase in AP-1 binding activity is also observed. The c-Jun protein is a major constituent of the AP-1 complex in quiescent and early regenerating liver. The activity of c-Jun nuclear kinase (JNK), which phosphorylates the activation domain of the c-Jun protein, is markedly stimulated after one-third PH. JNK1 or an immunologically related kinase is a constituent of this stimulated JNK activity after PH. When primary cultures of adult rat hepatocytes are incubated with epidermal growth factor or transforming growth factor-alpha, AP-1 transcriptional activity is increased and the activation domain of the c-Jun protein is further potentiated. Phosphopeptide mapping of the endogenous c-Jun protein in proliferating cultured hepatocytes demonstrates phosphorylation of the c-Jun activation domain. Combining the results of these in vivo and culture studies, we conclude that the minimal stimulation of one-third PH activates JNK, which phosphorylates the c-Jun activation domain in hepatocytes, resulting in enhanced transcription of AP-1-dependent genes.
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill 27599-7038.
authors.forename: J K
authors.initials: JK
authors.lastname: Westwick
authors.forename: C
authors.initials: C
authors.lastname: Weitzel
authors.forename: H L
authors.initials: HL
authors.lastname: Leffert
authors.forename: D A
authors.initials: DA
authors.lastname: Brenner
mesh_terms: D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D017364:Collagenases / Q000235:genetics; D016384:Consensus Sequence; D004789:Enzyme Activation; D004790:Enzyme Induction; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D006498:Hepatectomy; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D008115:Liver Regeneration; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011494:Protein Kinases / Q000096:biosynthesis*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000096:biosynthesis; D013997:Time Factors
chemical_list: D015345:Oligonucleotide Probes; D016755:Proto-Oncogene Proteins c-jun; D012709:Serum Albumin; D011494:Protein Kinases; D017364:Collagenases