Hormonal regulation of caveolae internalization.
Caveolae undergo a cyclic transition from a flat segment of membrane to a vesicle that then returns to the cell surface. Here we present evidence that this cycle depends on a population of protein kinase C-alpha (PKC-alpha) molecules that reside in the caveolae membrane where they phosphorylate a 90-kD protein. This cycle can be interrupted by treatment of the cells with phorbol-12,13-dibutyrate or agents that raise the concentration of diacylglycerol in the cell. Each of these conditions displaces PKC-alpha from caveolae, inhibits the phosphorylation of the 90-kD protein, and prevents internalization. Caveolae also contain a protein phosphatase that dephosphorylates the 90-kD once PKC-alpha is gone. A similar dissociation of PKC-alpha from caveolae and inhibition of invagination was observed when cells were treated with histamine. This effect was blocked by pyrilamine but not cimetidine, indicating the involvement of histamine H1 receptors. These findings suggest that the caveolae internalization cycle is hormonally regulated.
D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D002460:Cell Line / Q000502:physiology / Q000648:ultrastructure; D002462:Cell Membrane / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D005459:Fluorides / Q000494:pharmacology; D005492:Folic Acid / Q000378:metabolism; D000882:Haplorhini; D006632:Histamine / Q000502:physiology; D006728:Hormones / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism / Q000494:pharmacology; D051571:Protein Kinase C-alpha; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013347:Subcellular Fractions; D013379:Substrate Specificity
D017607:Aluminum Compounds; D006728:Hormones; D007527:Isoenzymes; D008565:Membrane Proteins; D017978:Receptors, Growth Factor; D015240:Phorbol 12,13-Dibutyrate; D006632:Histamine; D005492:Folic Acid; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D005459:Fluorides; C032311:aluminum fluoride