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Regulation of Discoidin Domain Receptor‐1 by Membrane‐type 1 Matrix Metalloproteinase (MT1‐MMP)
Author(s) -
Fu HsuehLiang,
Fridman Rafael
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.121.8
Subject(s) - matrix metalloproteinase , discoidin domain , ddr1 , metalloproteinase , receptor , matrix metalloproteinase 3 , domain (mathematical analysis) , matrix metalloproteinase 9 , chemistry , microbiology and biotechnology , biology , biochemistry , mathematics , receptor tyrosine kinase , mathematical analysis
Objective We investigated the effects of membrane type‐matrix metalloproteinases (MT‐MMPs) on the activation of discoidin domain receptors (DDRs), which are receptor tyrosine kinases (RTKs) that undergo receptor autophosphorylation in response to collagen. Methods Proteases were co‐expressed with DDR1a or DDR1b and receptor phosphorylation in response to collagen was examined. Results we found that the transmembrane MT‐MMPs, MT1‐(MMP14), MT2‐ (MMP15), and MT3‐ (MMP16) MMP but not other members of the MT‐MMP subfamily hinder collagen‐dependent DDR1a/b activation and promote cleavage of the receptor ectodomain. Two soluble collagenases, MMP1 and MMP13, and a chimeric MT1‐MMP containing the catalytic domain of MMP1 had no effect on DDR1 activation or cleavage, suggesting a specific effect of MT‐MMPs on DDR1 regulation. T47D breast cancer cells expressing recombinant MT1‐MMP exhibit reduced collagen‐dependent phosphorylation and increased cleavage of endogenous DDR1. Conclusion These results show that DDR1a/b activation is specifically regulated by MT‐MMPs and suggests that MT‐MMP/DDR interactions may play a role in regulation of cell‐collagen interactions during cell migration and invasion.