Discoidin domain receptor 1 controls growth and adhesion of mesangial cells.
Various types of collagen are known as modulators of mesangial cell proliferation. Here the function of the collagen-binding tyrosine kinase receptor discoidin domain receptor 1 (DDR1) in mesangial cells is investigated. The expression of DDR1 in the mouse kidney is confirmed by Northern analysis. In primary mesangial cells isolated from wild-type and DDR1-null mice, tyrosine phosphorylation in response to collagen-stimulation, adhesion to collagen, and cellular proliferation were measured. DDR1 phosphorylation was induced after overnight incubation of cells with type I collagen. Compared with wild-type cells, the adhesion of DDR1-null cells was drastically reduced. In contrast, DDR1-knockout cells showed significantly enhanced proliferation compared with wild-type cells. Both effects were largely independent of the collagen-binding alpha1/beta1 integrin function. This study found that the increased proliferation rate of DDR1-null cells is caused by a constitutive upregulation of p42/p44 and p38 mitogen-activated protein kinases (MAPK) activity. This is the first evidence indicating that DDR1 could be involved in the proliferative stage of renal disorders.
Curat
Cyrile A
CA
Georg-Speyer-Haus, Institute for Biomedical Research, Frankfurt am Main, Germany.
Vogel
Wolfgang F
WF
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D000070818:Discoidin Domain Receptors; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D011975:Receptors, Mitogen / Q000502:physiology*
D011975:Receptors, Mitogen; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases