Differential signaling and regulation of apical vs. basolateral EGFR in polarized epithelial cells.
Overexpression of the epidermal growth factor receptors (EGFR) in polarized kidney epithelial cells caused them to appear in high numbers at both the basolateral and apical cell surfaces. We utilized these cells to look for differences in the regulation and signaling of apical vs. basolateral EGFR. Apical and basolateral EGFR were biologically active and mediated EGF-induced cell proliferation to similar degrees. Receptor downregulation and endocytosis were less efficient at the apical surface, resulting in prolonged EGF-induced tyrosine kinase activity at the apical cell membrane. Tyrosine phosphorylation of EGFR substrates known to mediate cell proliferation, Src-homologous and collagen protein (SHC), extracellularly regulated kinase 1 (ERK1), and ERK2 could be induced similarly by activation of apical or basolateral EGFR. Focal adhesion kinase was tyrosine phosphorylated more by basolateral than by apical EGFR; however, beta-catenin was tyrosine phosphorylated to a much greater degree following the activation of mislocalized apical EGFR. Thus EGFR regulation and EGFR-mediated phosphorylation of certain substrates differ at the apical and basolateral cell membrane domains. This suggests that EGFR mislocalization could result in abnormal signal transduction and aberrant cell behavior.
Kuwada
S K
SK
Division of Gastroenterology, Departments of Medicine, Salt Lake City, Utah 84132, USA.
Lund
K A
KA
Li
X F
XF
Cliften
P
P
Amsler
K
K
Opresko
L K
LK
Wiley
H S
HS
D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism*; D018374:LLC-PK1 Cells; D015398:Signal Transduction / Q000502:physiology*; D013552:Swine
D066246:ErbB Receptors