Presence of oxidized cholesterol in caveolae uncouples active platelet-derived growth factor receptors from tyrosine kinase substrates.
Platelet-derived growth factor receptor beta (PDGFRbeta) in fibroblasts is concentrated in caveolae where it controls the tyrosine phosphorylation of multiple proteins. Caveolae are enriched in cholesterol and sphingolipids, but the role of these lipids in PDGFR signal transduction is unknown. We report that introduction of cholest-4-en-3-one into caveolae membranes uncouples PDGFR autophosphorylation from tyrosine phosphorylation of neighboring proteins. Cholest-4-en-3-one appears to interfere with the normal interaction between PDGFR and its partners. The results suggest that tightly packed caveolae lipids form a membrane platform that functions as a lipid scaffold for organizing the molecular interactions of multiple signaling pathways.
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA.
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P
Liu
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Wang
P
P
Michaely
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M
Zhu
R G
RG
Anderson
D021941:Caveolae / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D002783:Cholestenones / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002789:Cholesterol Oxidase / Q000378:metabolism; D005347:Fibroblasts; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D002783:Cholestenones; D008563:Membrane Lipids; D010982:Platelet-Derived Growth Factor; C000475:cholest-4-en-3-one; D002784:Cholesterol; D002789:Cholesterol Oxidase; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D010100:Oxygen