Rescue of W-associated mast cell defects in W/Wv bone marrow cells by ectopic expression of normal and mutant epidermal growth factor receptors.
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.
von Rüden
T
T
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
Stingl
L
L
Ullrich
A
A
Wagner
E F
EF
D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D007267:Injections; D007377:Interleukin-3 / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology* / Q000648:ultrastructure*; D008415:Mastocytosis / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains / Q000502:physiology*; D008934:Mitogens / Q000502:physiology; D010529:Peritoneal Cavity; D015398:Signal Transduction
D007377:Interleukin-3; D008934:Mitogens; D066246:ErbB Receptors