title: Signal transduction through the EGF receptor transfected in IL-3-dependent hematopoietic cells.
abstract: An expression vector for the epidermal growth factor (EGF) receptor was introduced into the 32D myeloid cell line, which is devoid of EGF receptors and absolutely dependent on interleukin-3 (IL-3) for its proliferation and survival. Expression of the EGF receptor conferred the ability to utilize EGF for transduction of a mitogenic signal. When the transfected cells were propagated in EGF, they exhibited a more mature myeloid phenotype than was observed under conditions of IL-3-directed growth. Moreover, exposure to EGF led to a rapid stimulation of phosphoinositide metabolism, while IL-3 had no detectable effect on phosphoinositide turnover either in control or EGF receptor-transfected 32D cells. Although the transfected cells exhibited high levels of functional EGF receptors, they remained nontumorigenic. In contrast, transfection of v-erbB, an amino-terminal truncated form of the EGF receptor with constitutive tyrosine kinase activity, not only abrogated the IL-3 growth factor requirement of 32D cells, but caused them to become tumorigenic in nude mice. These results show that a naïve hematopoietic cell expresses all of the intracellular components of the EGF-signaling pathway necessary to evoke a mitogenic response and sustain continuous proliferation.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
authors.forename: J H
authors.initials: JH
authors.lastname: Pierce
authors.forename: M
authors.initials: M
authors.lastname: Ruggiero
authors.forename: T P
authors.initials: TP
authors.lastname: Fleming
authors.forename: P P
authors.initials: PP
authors.lastname: Di Fiore
authors.forename: J S
authors.initials: JS
authors.lastname: Greenberger
authors.forename: L
authors.initials: L
authors.lastname: Varticovski
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
authors.forename: G
authors.initials: G
authors.lastname: Rovera
authors.forename: S A
authors.initials: SA
authors.lastname: Aaronson
mesh_terms: D000818:Animals; D002455:Cell Division; D002460:Cell Line; D003001:Cloning, Molecular; D004261:DNA Replication / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007377:Interleukin-3 / Q000494:pharmacology*; D014162:Transfection
chemical_list: D007377:Interleukin-3; D004815:Epidermal Growth Factor; D066246:ErbB Receptors