In situ activation pattern of Met docking site following renal injury and hypertrophy

Benjamin Dekel, Sharon Biton, Gil M. Yerushalmi, Rom T. Altstock, Leonid Mittelman, Donna Faletto, Nechama I. Smordinski, Ian Tsarfaty

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 6h 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). Interestingly, the stimulus for hypertrophy in the remnant kidney after uninephrectomy and the contralateral kidney during ischaemia is not accompanied 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.

Original languageEnglish (US)
Pages (from-to)1493-1504
Number of pages12
JournalNephrology Dialysis Transplantation
Volume18
Issue number8
DOIs
StatePublished - Aug 1 2003

Fingerprint

Hypertrophy
Kidney
Wounds and Injuries
Hepatocyte Growth Factor
Ischemia
Up-Regulation
Kidney Medulla
Staining and Labeling
Kidney Cortex
Growth Factor Receptors
Receptor Protein-Tyrosine Kinases
Pathologic Processes
Indirect Fluorescent Antibody Technique
Nephrectomy
Transducers
Morphogenesis
Confocal Microscopy
Protein-Tyrosine Kinases
Cell Movement
Tyrosine

Keywords

  • HGF/SF
  • Ischaemia
  • Met
  • Signal transduction
  • Tyrosine kinase docking site

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Dekel, B., Biton, S., Yerushalmi, G. M., Altstock, R. T., Mittelman, L., Faletto, D., ... Tsarfaty, I. (2003). In situ activation pattern of Met docking site following renal injury and hypertrophy. Nephrology Dialysis Transplantation, 18(8), 1493-1504. https://doi.org/10.1093/ndt/gfg215

In situ activation pattern of Met docking site following renal injury and hypertrophy. / Dekel, Benjamin; Biton, Sharon; Yerushalmi, Gil M.; Altstock, Rom T.; Mittelman, Leonid; Faletto, Donna; Smordinski, Nechama I.; Tsarfaty, Ian.

In: Nephrology Dialysis Transplantation, Vol. 18, No. 8, 01.08.2003, p. 1493-1504.

Research output: Contribution to journalArticle

Dekel, B, Biton, S, Yerushalmi, GM, Altstock, RT, Mittelman, L, Faletto, D, Smordinski, NI & Tsarfaty, I 2003, 'In situ activation pattern of Met docking site following renal injury and hypertrophy', Nephrology Dialysis Transplantation, vol. 18, no. 8, pp. 1493-1504. https://doi.org/10.1093/ndt/gfg215
Dekel, Benjamin ; Biton, Sharon ; Yerushalmi, Gil M. ; Altstock, Rom T. ; Mittelman, Leonid ; Faletto, Donna ; Smordinski, Nechama I. ; Tsarfaty, Ian. / In situ activation pattern of Met docking site following renal injury and hypertrophy. In: Nephrology Dialysis Transplantation. 2003 ; Vol. 18, No. 8. pp. 1493-1504.
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AU - Dekel, Benjamin

AU - Biton, Sharon

AU - Yerushalmi, Gil M.

AU - Altstock, Rom T.

AU - Mittelman, Leonid

AU - Faletto, Donna

AU - Smordinski, Nechama I.

AU - Tsarfaty, Ian

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N2 - 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 6h 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). Interestingly, the stimulus for hypertrophy in the remnant kidney after uninephrectomy and the contralateral kidney during ischaemia is not accompanied 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.

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 6h 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). Interestingly, the stimulus for hypertrophy in the remnant kidney after uninephrectomy and the contralateral kidney during ischaemia is not accompanied 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.

KW - HGF/SF

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KW - Signal transduction

KW - Tyrosine kinase docking site

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