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Generation, Purification, and Characterization of Cell-invasive DISC1 Protein Species
14:33

Generation, Purification, and Characterization of Cell-invasive DISC1 Protein Species

Published on: August 30, 2012

Ligand-induced shedding of discoidin domain receptor 1

Wolfgang F Vogel1

  • 1Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Medical Science Building, Room 7334A, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8. w.vogel@utoronto.ca

FEBS Letters
|April 12, 2002
PubMed

Insights

Discoidin domain receptor 1 (DDR1) shedding is identified, revealing a 62 kDa C-terminal fragment. This shedding process, inhibited by matrix metalloproteinase inhibitors, suggests a novel regulatory mechanism for DDR1 tyrosine kinases.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Biochemistry

Background:

  • Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagen.
  • DDR1 plays roles in cell adhesion, migration, and proliferation.
  • The regulation of DDR1 activity, particularly its extracellular shedding, is not fully understood.

Purpose of the Study:

  • To identify and characterize a novel protein co-purifying with DDR1.
  • To investigate the mechanism of DDR1 shedding.
  • To identify the enzyme responsible for DDR1 shedding.

Main Methods:

  • Immunoprecipitation of DDR1 using a juxtamembrane-specific antibody.
  • Co-purification and identification of a 62 kDa protein.
  • Inhibition studies using furin and matrix metalloproteinase inhibitors.

Main Results:

  • A 62 kDa tyrosine-phosphorylated protein was identified as a C-terminal cleavage product of DDR1.
  • DDR1 shedding was partially inhibited by a furin inhibitor and completely inhibited by batimastat.
  • The DDR1 sheddase is suggested to be a matrix metalloproteinase or a disintegrin and metalloproteinase family member.

Conclusions:

  • A novel DDR1 shedding mechanism has been discovered.
  • The shedding process generates a C-terminal fragment of DDR1.
  • The enzyme responsible for DDR1 shedding likely belongs to the metalloproteinase family, suggesting a new regulatory pathway for DDR1 signaling.

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