EGF receptor and erbB-2 tyrosine kinase domains confer cell specificity for mitogenic signaling.
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.
Di Fiore
P P
PP
Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Segatto
O
O
Taylor
W G
WG
Aaronson
S A
SA
Pierce
J H
JH
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004274:DNA, Recombinant; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D008934:Mitogens; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D014162:Transfection
D004274:DNA, Recombinant; D008934:Mitogens; D011518:Proto-Oncogene Proteins; D004247:DNA; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases