PMID- 15249655
OWN - NLM
STAT- MEDLINE
DCOM- 20040826
LR  - 20220408
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 101
IP  - 29
DP  - 2004 Jul 20
TI  - Met provides essential signals for liver regeneration.
PG  - 10608-13
AB  - Genetic analysis in mice has demonstrated a crucial role of the Met tyrosine 
      kinase receptor and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), 
      in development of the liver, muscle, and placenta. Here, we use conditional 
      mutagenesis in mice to analyze the function of Met during liver regeneration, 
      using the Mx-cre transgene to introduce the mutation in the adult. After partial 
      hepatectomy in mice carrying the Mx-cre-induced Met mutation, regeneration of the 
      liver is impaired. Comparison of signal transduction pathways in control and 
      mutant livers indicates that Met and other signaling receptors cooperate to fully 
      activate particular signaling molecules, for instance, the protein kinase Akt. 
      However, activation of the Erk1/2 kinase during liver regeneration depends 
      exclusively on Met. Signaling crosstalk is thus an important aspect of the 
      regulation of liver regeneration. Analysis of cell cycle progression of 
      hepatocytes in conditional Met mutant mice indicates a defective exit from 
      quiescence and diminished entry into S phase. Impaired liver regeneration is 
      accompanied by compensatory physiological responses that include prolonged 
      up-regulation of HGF/SF and IL-6 in peripheral blood. Our data demonstrate that 
      the HGF/SF/Met signaling system is essential not only during liver development 
      but also for the regeneration of the organ in the adult.
FAU - Borowiak, Malgorzata
AU  - Borowiak M
AD  - Max Delbruck Center for Molecular Medicine, Robert-Rossle-Strasse 10, 13125 
      Berlin-Buch, Germany.
FAU - Garratt, Alistair N
AU  - Garratt AN
FAU - Wustefeld, Torsten
AU  - Wustefeld T
FAU - Strehle, Michael
AU  - Strehle M
FAU - Trautwein, Christian
AU  - Trautwein C
FAU - Birchmeier, Carmen
AU  - Birchmeier C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040712
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - Cell Cycle/physiology
MH  - Cell Cycle Proteins/metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Hepatectomy
MH  - Hepatocyte Growth Factor/blood
MH  - Interleukin-6/blood
MH  - Liver/cytology/metabolism/pathology
MH  - *Liver Regeneration
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Mutation
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogene Proteins c-met/genetics/*metabolism
MH  - STAT3 Transcription Factor
MH  - Signal Transduction/*physiology
MH  - Trans-Activators/metabolism
MH  - Transgenes
PMC - PMC490025
EDAT- 2004/07/14 05:00
MHDA- 2004/08/27 05:00
PMCR- 2005/01/20
CRDT- 2004/07/14 05:00
PHST- 2004/07/14 05:00 [pubmed]
PHST- 2004/08/27 05:00 [medline]
PHST- 2004/07/14 05:00 [entrez]
PHST- 2005/01/20 00:00 [pmc-release]
AID - 0403412101 [pii]
AID - 10110608 [pii]
AID - 10.1073/pnas.0403412101 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10608-13. doi: 
      10.1073/pnas.0403412101. Epub 2004 Jul 12.