PMID- 12897086
OWN - NLM
STAT- MEDLINE
DCOM- 20031117
LR  - 20190513
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 18
IP  - 8
DP  - 2003 Aug
TI  - In situ activation pattern of Met docking site following renal injury and 
      hypertrophy.
PG  - 1493-504
AB  - BACKGROUND: Hepatocyte growth factor/scatter factor (HGF/SF) binds to its 
      tyrosine kinase receptor, Met, thereby stimulating diverse cellular responses. 
      The multifunctional docking site in the C-terminal domain mediates the signal of 
      phosphorylated Met receptors to multiple transducers. The tyrosine at position 
      1356 of the Met docking site is crucial for cell motility and morphogenesis. 
      METHODS: We examined the in situ distribution patterns of the 
      Tyr1356-phosphorylated form of Met with a novel monoclonal antibody following 
      renal injury and renal hypertrophy in rats. Sections of the kidney following 
      either sham operation, transient ischaemia of one kidney or unilateral 
      nephrectomy were analysed using indirect immunofluorescence staining and confocal 
      laser scanning microscopy analysis of total Met protein levels and 
      Tyr1356-phosphorylated Met (Met and pMet, respectively). RESULTS: At 6 h 
      post-treatment, pMet increases in ischaemic kidneys compared with sham-operated 
      kidneys, and these changes become substantial after 48 h in both medulla and 
      cortex of ischaemic kidneys (P < 0.001). We also show significant up-regulation 
      of Met predominantly in the medulla of ischaemic kidneys, 48 h following injury 
      (P < 0.009). Inter-estingly, the stimulus for hypertrophy in the remnant kidney 
      after uninephrectomy and the contra-lateral kidney during ischaemia is not 
      accom-panied by significant up-regulation of Met or pMet staining compared with 
      sham operation at both time points. CONCLUSIONS: We demonstrate in this work, for 
      the first time, in situ detection of tyrosine kinase growth factor receptor 
      docking site activation during pathological processes in the kidney. Using this 
      methodology, we show a significant increase in Met docking site activity in both 
      renal medulla and cortex solely following stimulation by ischaemia and repair.
FAU - Dekel, Benjamin
AU  - Dekel B
AD  - Department of Pediatrics, Chaim Sheba Medical Center, Tel Hashomer, Sackler 
      School of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Biton, Sharon
AU  - Biton S
FAU - Yerushalmi, Gil M
AU  - Yerushalmi GM
FAU - Altstock, Rom T
AU  - Altstock RT
FAU - Mittelman, Leonid
AU  - Mittelman L
FAU - Faletto, Donna
AU  - Faletto D
FAU - Smordinski, Nechama I
AU  - Smordinski NI
FAU - Tsarfaty, Ilan
AU  - Tsarfaty I
LA  - eng
PT  - Journal Article
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Antibodies, Monoclonal)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal
MH  - Binding Sites
MH  - Hepatocyte Growth Factor/*metabolism
MH  - Hyperplasia
MH  - Hypertrophy
MH  - Kidney Cortex/*pathology/physiopathology
MH  - Kidney Medulla/*pathology/physiopathology
MH  - Male
MH  - Microscopy, Confocal
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-met/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/physiology
MH  - Up-Regulation/physiology
EDAT- 2003/08/05 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/08/05 05:00
PHST- 2003/08/05 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/08/05 05:00 [entrez]
AID - 10.1093/ndt/gfg215 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2003 Aug;18(8):1493-504. doi: 10.1093/ndt/gfg215.