Extracellular matrix components cooperate to activate phosphatidyl inositol-4-phosphate 5-kinase.
Interaction of mesangial cells with extracellular matrix proteins can provide a means to modify cellular anchorage and traction through an interaction of integrins with activation of the actin cytoskeleton. We investigated intracellular signalling of matrix components fibronectin and laminin in mesangial cells in monolayer and 3-dimensional configurations to show a fibronectin-dependent activation of phosphatidylinositol-4-phosphate 5-kinase (up to threefold), which is augmented by a laminin-dependent increase in phospholipase D activity. Functional responsiveness to fibronectin and laminin addition was seen in the contraction of free-floating 3-dimensional mesangial cell-embedded collagen gels, a well-defined system reflecting coupling of extracellular matrix-cell events to activation of the actin cytoskeleton. Activation of phosphatidylinositol-4-phosphate 5-kinase and contraction of mesangial cell-embedded collagen gels in response to fibronectin and laminin were inhibited by pretreatment of mesangial cells with lovastatin and restored by isoprenoid augmentation with geranylgeraniol, supporting a role for the ras-related protein Rho in this process.
Dunlop
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Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia. medunlop@unimelb.edu.au
Muggli
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D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D007797:Laminin / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D017368:Protein Prenylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D000924:Anticholesteremic Agents; D005353:Fibronectins; D007797:Laminin; D018129:Phosphatidylinositol Phosphates; D011106:Polyisoprenyl Phosphates; D003094:Collagen; D008148:Lovastatin; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D010739:Phospholipase D