PMID- 10635333 OWN - NLM STAT- MEDLINE DCOM- 20000131 LR - 20190915 IS - 1097-2765 (Print) IS - 1097-2765 (Linking) VI - 4 IP - 6 DP - 1999 Dec TI - Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBP beta is required for hepatocyte proliferation induced by TGF alpha. PG - 1087-92 AB - 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. FAU - Buck, M AU - Buck M AD - Salk Institute for Biological Studies, La Jolla, California 92037, USA. mbuck@salk.edu FAU - Poli, V AU - Poli V FAU - van der Geer, P AU - van der Geer P FAU - Chojkier, M AU - Chojkier M FAU - Hunter, T AU - Hunter T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell JT - Molecular cell JID - 9802571 RN - 0 (CCAAT-Enhancer-Binding Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Transforming Growth Factor alpha) RN - 2ZD004190S (Threonine) RN - 452VLY9402 (Serine) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases) SB - IM MH - Amino Acid Sequence MH - Animals MH - CCAAT-Enhancer-Binding Proteins MH - Cell Division/drug effects/physiology MH - DNA-Binding Proteins/*physiology MH - Enzyme Activation MH - Female MH - Liver/*pathology/*physiology MH - Mice MH - Molecular Sequence Data MH - Nuclear Proteins/*physiology MH - Phosphorylation MH - Rats MH - Rats, Sprague-Dawley MH - Ribosomal Protein S6 Kinases/*physiology MH - Serine MH - Signal Transduction/*drug effects MH - Threonine MH - Transforming Growth Factor alpha/*pharmacology EDAT- 2000/01/15 00:00 MHDA- 2000/01/15 00:01 CRDT- 2000/01/15 00:00 PHST- 2000/01/15 00:00 [pubmed] PHST- 2000/01/15 00:01 [medline] PHST- 2000/01/15 00:00 [entrez] AID - S1097-2765(00)80237-3 [pii] AID - 10.1016/s1097-2765(00)80237-3 [doi] PST - ppublish SO - Mol Cell. 1999 Dec;4(6):1087-92. doi: 10.1016/s1097-2765(00)80237-3.