Transfer of functional EGF receptors to an IL3-dependent cell line.
Epidermal growth factor (EGF) is a small protein that acts as a mitogen for various epidermal, epithelial, and fibroblastic cells that bear specific EGF receptors. The molecule that binds EGF is a 175-kD transmembrane protein, with an extracellular ligand binding domain and an intracellular domain that possesses tyrosine kinase activity, thought to be involved in the mitogenic signalling process. Here we have constructed a recombinant murine retrovirus that transduces a human cDNA encoding the 175-kD protein and used this retrovirus to infect BAF3, a murine, bone marrow-derived cell line, which is dependent on the haematopoietic factor interleukin-3 (IL3) for its growth in culture. The EGF receptors expressed in the infected cells exhibit two affinity states, as well as EGF-stimulated autophosphorylation. Furthermore, EGF can replace IL3 in supporting short-term proliferation of these cells. These data identify functional properties of the EGF receptor upon expression of the 175-kD EGF binding protein in a haemotopoietic cell that does not express endogenous receptors. They also suggest that gene transfer of growth factor receptors to heterologous cells may allow novel growth stimuli to be exploited.
Collins
M K
MK
Whitehead Institute, Cambridge, Massachusetts 02142.
Downward
J
J
Miyajima
A
A
Maruyama
K
K
Arai
K
K
Mulligan
R C
RC
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D008970:Molecular Weight; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic
D007377:Interleukin-3; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases