title: Cell adhesion to fibronectin regulates membrane lipid biosynthesis through 5'-AMP-activated protein kinase.
abstract: We have shown that attachment to a fibronectin substrate stimulates two pathways of lipid biosynthesis in cultured human fibroblasts. Detachment of these cells (mechanically, with trypsin, or by RGDS peptides) caused a significant decrease in their 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and in their incorporation of [3H]acetate into fatty acids. This inhibition was substantially reversed by the reattachment of cells to fibronectin substrates, but not to poly-L-lysine substrates or to fibronectin in solution. Inhibiting phosphoprotein phosphatase activity with okadaic acid blocked the recovery of both biosynthetic activities. Both 3-hydroxy-3-methylglutaryl-coenzyme A reductase and fatty acid biosynthesis are known to be inhibited by the action of 5'-AMP-activated protein kinase, which is activated by an increase in the level of AMP relative to ATP. For example, in our system, sodium azide and 2-deoxy-D-glucose increased the ratio of cellular AMP to ATP and caused a decrease in lipid biosynthesis. We then verified the prediction that detachment of cells from substrates also caused an increase in the AMP/ATP ratio. We therefore conclude that the attachment of cells to fibronectin promotes lipid biosynthesis, presumably in coordination with the cellular growth response evoked by attachment to the extracellular matrix.
authors.affiliation: Department of Biochemistry, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
authors.forename: K
authors.initials: K
authors.lastname: Page
authors.forename: Y
authors.initials: Y
authors.lastname: Lange
mesh_terms: D055372:AMP-Activated Protein Kinases; D000249:Adenosine Monophosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D002448:Cell Adhesion; D002478:Cells, Cultured; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008563:Membrane Lipids / Q000096:biosynthesis*; D009097:Multienzyme Complexes / Q000502:physiology*; D019319:Okadaic Acid / Q000494:pharmacology; D009842:Oligopeptides / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases
chemical_list: D005353:Fibronectins; D008563:Membrane Lipids; D009097:Multienzyme Complexes; D009842:Oligopeptides; D019319:Okadaic Acid; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; C046617:arginyl-glycyl-aspartyl-serine; D006903:Hydroxymethylglutaryl CoA Reductases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases