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  • 1
    Publication Date: 1990-04-06
    Description: The epidermal growth factor (EGF) receptor (EGFR) can efficiently couple with mitogenic signaling pathways when it is transfected into interleukin-3 (IL-3)-dependent 32D hematopoietic cells. When expression vectors for erbB-2, which is structurally related to EGFR, or its truncated counterpart, delta NerbB-2, were introduced into 32D cells, neither was capable of inducing proliferation. This was despite overexpression and constitutive tyrosine kinase activity of their products at levels associated with potent transformation of fibroblast target cells. Thus, EGFR and erbB-2 couple with distinct mitogenic signaling pathways. The region responsible for the specificity of intracellular signal transduction was localized to a 270-amino acid stretch encompassing their respective tyrosine kinase domains. Thus, tissue- or cell-specific regulation of growth factor receptor signaling can occur at a point after the initial interaction of growth factor with receptor. Such specificity in signal transduction may account for the selection of certain oncogenes in some malignancies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Di Fiore, P P -- Segatto, O -- Taylor, W G -- Aaronson, S A -- Pierce, J H -- New York, N.Y. -- Science. 1990 Apr 6;248(4951):79-83.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2181668" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Division ; Cell Line ; DNA/genetics ; DNA, Recombinant ; Fibroblasts/cytology/metabolism ; Gene Expression ; Genetic Vectors ; Hematopoietic Stem Cells/cytology/metabolism ; Immunoblotting ; Mice ; *Mitogens ; Molecular Sequence Data ; Protein-Tyrosine Kinases/genetics/*physiology ; Proto-Oncogene Proteins/genetics/*physiology ; Receptor, Epidermal Growth Factor/genetics/*physiology ; Sequence Homology, Nucleic Acid ; Signal Transduction ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1988-02-05
    Description: 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 naive hematopoietic cell expresses all of the intracellular components of the EGF-signaling pathway necessary to evoke a mitogenic response and sustain continuous proliferation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pierce, J H -- Ruggiero, M -- Fleming, T P -- Di Fiore, P P -- Greenberger, J S -- Varticovski, L -- Schlessinger, J -- Rovera, G -- Aaronson, S A -- New York, N.Y. -- Science. 1988 Feb 5;239(4840):628-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3257584" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Line ; *Cloning, Molecular ; DNA Replication/drug effects ; Epidermal Growth Factor/metabolism/pharmacology ; Genetic Vectors ; Hematopoietic Stem Cells/cytology/drug effects/*metabolism ; Interleukin-3/*pharmacology ; Receptor, Epidermal Growth Factor/*genetics/metabolism ; *Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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