Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBP beta is required for hepatocyte proliferation induced by TGF alpha

Mol Cell. 1999 Dec;4(6):1087-92. doi: 10.1016/s1097-2765(00)80237-3.


We report that TGF alpha induces activation of the p90 ribosomal S kinase (RSK), which results in the phosphorylation of rat C/EBP beta on Ser-105 and of mouse C/EBP beta on Thr-217 and concomitantly stimulates proliferation in differentiated hepatocytes. Moreover, C/EBP beta-/- mouse hepatocytes respond to TGF alpha when wild-type C/EBP beta is reexpressed, whereas they remain refractory to the growth effect of TGF alpha when expressing phosphoacceptor mutants rat C/EBP beta Ala-105 or mouse C/EBP beta Ala-217. In contrast, C/EBP beta-/- hepatocytes expressing the phosphorylation mimic mutants, rat C/EBP beta Asp-105 or mouse C/EBP beta Glu-217, exhibited marked proliferation in the absence of TGF alpha. Thus, a site-specific phosphorylation of the transcription factor C/EBP beta is critical for hepatocyte proliferation induced by TGF alpha and other stimuli that activate RSK.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CCAAT-Enhancer-Binding Proteins
  • Cell Division / drug effects
  • Cell Division / physiology
  • DNA-Binding Proteins / physiology*
  • Enzyme Activation
  • Female
  • Liver / pathology*
  • Liver / physiology*
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / physiology*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Ribosomal Protein S6 Kinases / physiology*
  • Serine
  • Signal Transduction / drug effects*
  • Threonine
  • Transforming Growth Factor alpha / pharmacology*


  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transforming Growth Factor alpha
  • Threonine
  • Serine
  • Ribosomal Protein S6 Kinases