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J. Biol. Chem., Vol. 277, Issue 28, 24843-24846, July 12, 2002
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From the Department of Cell Biology, University of Texas
Southwestern Medical Center, Dallas, Texas 75235-9039
Previous studies have shown that ~60% of the
epidermal growth factor receptors (EGFRs) in quiescent
fibroblasts are concentrated in the caveolae/raft 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 was sufficient
to target the transmembrane and cytoplasmic tails of both EGFR and the
low density lipoprotein receptor to caveolae/rafts. Two
N-linked sugars in this segment were not required for
proper targeting, although unglycosylated wild-type receptors did not
localize properly. We conclude that, in contrast to signals for coated
pit localization that are in the cytoplasmic tail, the targeting
information for caveolae/rafts is on the extracellular side of the EGFR
very close to the membrane.
To whom correspondence should be addressed. Tel.: 214-648-2346;
Fax: 214-648-7577; E-mail: richard.anderson@utsouthwestern.edu.
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