The Epidermal Growth Factor Receptor Juxtamembrane Domain Has Multiple Basolateral Plasma Membrane Localization Determinants, Including a Dominant Signal with a Polyproline Core

• DOI: 10.1074/jbc.m104646200
• Publication Date: 2002-10-07T21:03:54Z
• Authors: Cheng He; Michael Hobert; Leslie Friend; Cathleen Carlin
• Keywords: Epithelial polarity; Polyproline helix

The epidermal growth factor (EGF) receptor is located predominantly in the basolateral membrane of polarized epithelia, where it plays a pivotal role during organogenesis and tissue homeostasis. We have shown previously that 22-amino acid sequence EGF juxtamembrane domain contains autonomous sorting information necessary for localization using Madin-Darby canine kidney epithelial cell model. goal this study was to determine molecular basis expression site-directed mutagenesis modify specific residues region. now show has two different, functionally redundant signals with distinct amino requirements: one dependent on residues⁶⁵⁸LL⁶⁵⁹ conforming well-characterized leucine-based signals, second containing polyproline core comprising Pro⁶⁶⁷ Pro⁶⁷⁰(⁶⁶⁷P<i>XX</i>P⁶⁷⁰). Our data also suggest Arg⁶⁶² contributes function proline-based signal. ⁶⁶⁷P<i>XX</i>P⁶⁷⁰was dominant signal when both motifs were present more effective than ⁶⁵⁸LL⁶⁵⁹ at overriding strong apical same molecule. Site-directed mutations Arg⁶⁶², Pro⁶⁶⁷, Pro⁶⁷⁰ associated increased full-length receptors, demonstrating first time region accurate native