PMID- 9166406
OWN - NLM
STAT- MEDLINE
DCOM- 19970630
LR  - 20211203
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 137
IP  - 5
DP  - 1997 Jun 2
TI  - A natural hepatocyte growth factor/scatter factor autocrine loop in myoblast 
      cells and the effect of the constitutive Met kinase activation on myogenic 
      differentiation.
PG  - 1057-68
AB  - As a rule, hepatocyte growth factor/scatter factor (HGF/SF) is produced by 
      mesenchymal cells, while its receptor, the tyrosine kinase encoded by the met 
      proto-oncogene, is expressed by the neighboring epithelial cells in a canonical 
      paracrine fashion. In the present work we show that both HGF/SF and met are 
      coexpressed by undifferentiated C2 mouse myoblasts. In growing cells, the 
      autocrine loop is active as the receptor exhibits a constitutive phosphorylation 
      on tyrosine that can be abrogated by exogenously added anti-HGF/SF neutralizing 
      antibodies. The transcription of HGF/SF and met genes is downregulated when 
      myoblasts stop proliferating and differentiate. The coexpression of HGF/SF and 
      met genes is not exclusive to C2 cells since it has been assessed also in other 
      myogenic cell lines and in mouse primary satellite cells, suggesting that HGF/SF 
      could play a role in muscle development through an autocrine way. To analyze the 
      biological effects of HGF/SF receptor activation, we stably expressed the 
      constitutively activated receptor catalytic domain (p65(tpr-met)) in C2 cells. 
      This active kinase determined profound changes in cell shape and inhibited 
      myogenesis at both morphological and biochemical levels. Notably, a complete 
      absence of muscle regulatory markers such as MyoD and myogenin was observed in 
      p65(tpr-met) highly expressing C2 clones. We also studied the effects of the 
      ectopic expression of human isoforms of met receptor (h-met) and of HGF/SF 
      (h-HGF/SF) in stable transfected C2 cells. Single constitutive expression of 
      h-met or h-HGF/SF does not alter substantially the growth and differentiation 
      properties of the myoblast cells, probably because of a species-specific 
      ligand-receptor interaction. A C2 clone expressing simultaneously both h-met and 
      h-HGF/SF is able to grow in soft agar and shows a decrease in myogenic potential 
      comparable to that promoted by p65(tpr-met) kinase. These data indicate that a 
      met kinase signal released from differentiation-dependent control provides a 
      negative stimulus for the onset of myogenic differentiation.
FAU - Anastasi, S
AU  - Anastasi S
AD  - Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biotecnologie 
      Cellulari ed Ematologia, Sezione di Genetica Molecolare, Universita di Roma La 
      Sapienza, 00161 Roma, Italy.
FAU - Giordano, S
AU  - Giordano S
FAU - Sthandier, O
AU  - Sthandier O
FAU - Gambarotta, G
AU  - Gambarotta G
FAU - Maione, R
AU  - Maione R
FAU - Comoglio, P
AU  - Comoglio P
FAU - Amati, P
AU  - Amati P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (MAS1 protein, human)
RN  - 0 (MYOG protein, human)
RN  - 0 (MyoD Protein)
RN  - 0 (Myog protein, mouse)
RN  - 0 (Myogenin)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - EC 2.7.- (Phosphotransferases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/physiology
MH  - Dogs
MH  - Down-Regulation/physiology
MH  - Enzyme Activation
MH  - Gene Expression/physiology
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/genetics/metabolism
MH  - Hepatocyte Growth Factor/*pharmacology
MH  - Humans
MH  - Kidney Tubules, Distal/cytology
MH  - Liver/cytology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Muscles/chemistry/*cytology/enzymology
MH  - MyoD Protein/genetics/metabolism
MH  - Myogenin/genetics/metabolism
MH  - Phosphotransferases/*metabolism
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins c-met
MH  - RNA, Messenger/metabolism
MH  - Receptor Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Species Specificity
MH  - Teratocarcinoma
MH  - Transfection
MH  - Tumor Cells, Cultured/drug effects/enzymology
PMC - PMC2136220
EDAT- 1997/06/02 00:00
MHDA- 1997/06/02 00:01
PMCR- 1997/12/02
CRDT- 1997/06/02 00:00
PHST- 1997/06/02 00:00 [pubmed]
PHST- 1997/06/02 00:01 [medline]
PHST- 1997/06/02 00:00 [entrez]
PHST- 1997/12/02 00:00 [pmc-release]
AID - 10.1083/jcb.137.5.1057 [doi]
PST - ppublish
SO  - J Cell Biol. 1997 Jun 2;137(5):1057-68. doi: 10.1083/jcb.137.5.1057.