Extracellular matrix modulates epidermal growth factor receptor activation in rat glomerular epithelial cells.
To understand how glomerular epithelial cell (GEC) proliferation may be regulated in health and disease, we studied the effects of type I collagen extracellular matrices (ECM) on EGF receptor (EGF-R) activation in cultured rat GEC. EGF stimulated proliferation of GEC adherent to ECM, but not of GEC on a plastic substratum. Significant and prolonged EGF-R tyrosine autophosphorylation (which reflects receptor kinase activation) was induced by EGF in GEC adherent to collagen, but EGF did not stimulate EGF-R autophosphorylation in GEC on plastic (at 37 degrees C). However, EGF-R autophosphorylation increased significantly in plastic-adherent GEC that were stimulated with EGF at 4 degrees C or in the presence of vanadate, an inhibitor of phosphotyrosine phosphatases. Furthermore, dephosphorylation of EGF-R was enhanced in GEC on plastic as compared with collagen. At 4 degrees C, [125I]EGF binding was not different between substrata, and there was negligible accumulation of intracellular [125I]EGF (which reflects EGF-R internalization). At 37 degrees C, EGF-R internalization was reduced significantly in collagen-adherent GEC as compared with GEC on plastic. Thus, contact with ECM facilitates proliferation and EGF-R activation in GEC. The enhanced activity of EGF-R tyrosine kinase may be due to ECM-induced reduction in EGF-R internalization and dephosphorylation by phosphotyrosine phosphatase(s). Signals from ECM to growth factor receptors may regulate cell turnover in the glomerulus under normal conditions and during immune glomerular injury.
Cybulsky
A V
AV
Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
McTavish
A J
AJ
Cyr
M D
MD
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism*; D005109:Extracellular Matrix / Q000502:physiology*; D007678:Kidney Glomerulus / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism
D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases