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Papers In Press, published online ahead of print May 21, 2002
J. Biol. Chem, 10.1074/jbc.C200277200
Submitted on May 7, 2002
Revised on May 21, 2002
Accepted on May 21, 2002
Department of Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390
Corresponding Author: richard.anderson{at}utsouthwestern.edu
Previous studies have shown that ~60% of the EGF receptors in quiescent fibroblasts are concentrated in the caveolae/rafts fraction from purified plasma membranes. This high degree of localization suggests the EGFR contains targeting information for lipid domains. We have used mutagenesis to determine that the region of the receptor that controls targeting to caveolae/rafts resides in the juxtamembrane, second cysteine-rich region. A 60 amino acid long sequence within this region that is continuous with the transmembrane domain is sufficient to target the transmembrane and cytoplasmic tails of both EGFR and the LDL receptor to caveolae/rafts. Two N-linked sugars in this segment are not required for proper targeting, although unglycosylated wild-type receptors do not localize properly. We conclude that in contrast to signals for coated pit localization, which are in the cytoplasmic tail, the targeting information for caveolae/rafts is on the extracellular side of the EGFR, very close to the membrane.
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