Rescue of W-associated mast cell defects in W/Wv bone marrow cells by
ectopic expression of normal and mutant epidermal growth factor receptors
T von Ruden, L Stingl, A Ullrich and EF Wagner
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
The normal human epidermal growth factor receptor (EGF-R) (HERc), a
chimeric EGF-R/v-erbB (HERerbB) receptor, and the ligand-independent
oncogenic EGF-R variant (v-erbB) were used to correct the mast cell defects
in W/Wv bone marrow (BM) cells. In culture, all three receptor molecules
transduced functional mitogenic signals in infected interleukin-3
(IL-3)-dependent bone marrow-derived mast cells (BMMCs) and enabled their
differentiation into safranin-positive mast cells resembling connective
tissue-type mast cells (CTMCs). Furthermore, expression of these receptors
restored the capacity of W/Wv BMMCs to colonize the peritoneal cavity of
mast cell-deficient W/Wv mice where they differentiated to
safranin-positive cells with similar frequencies as wild-type BMMCs. These
experiments show that expression of normal and mutant EGF-Rs in W/Wv BM
cells is able to complement the function of the c-kit-encoded Steel factor
receptor (SLF-R) in mast cell development. We conclude that signal
transduction by normal and mutant EGF-Rs in murine hematopoietic cells
apparently involves components also used by the SLF-R, which suggests that
these receptors use overlapping pathways for signal transduction.
Volume 82,
Issue 5,
pp. 1463-1470,
09/01/1993
Copyright © 1993 by The American Society of Hematology
