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J. Cell Biol.,
Volume 141, Number 3, May 4, 1998 601-610
to Caveolae


* Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9039;
and Previously, we showed caveolae contain a
population of protein kinase C
Adirondack Biomedical Research Institute, Lake Placid, New York 12946
(PKC
) that appears
to regulate membrane invagination. We now report
that multiple PKC isoenzymes are enriched in caveolae of unstimulated fibroblasts. To understand the mechanism of PKC targeting, we prepared caveolae lacking
PKC
and measured the interaction of recombinant
PKC
with these membranes. PKC
bound with high
affinity and specificity to caveolae membranes. Binding was calcium dependent, did not require the addition of
factors that activate the enzyme, and involved the regulatory domain of the molecule. A 68-kD PKC
-binding
protein identified as sdr (serum deprivation response)
was isolated by interaction cloning and localized to caveolae. Antibodies against sdr inhibited PKC
binding. A 100-amino acid sequence from the middle of sdr
competitively blocked PKC
binding while flanking sequences were inactive. Caveolae appear to be a membrane site where PKC enzymes are organized to carry
out essential regulatory functions as well as to modulate signal transduction at the cell surface.
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