Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 5 February 1988:
Vol. 239. no. 4840, pp. 628 - 631
DOI: 10.1126/science.3257584
Prev | Table of Contents | Next

Articles

Science, Vol 239, Issue 4840, 628-631
Copyright © 1988 by American Association for the Advancement of Science

articles

Signal transduction through the EGF receptor transfected in IL-3-dependent hematopoietic cells

JH Pierce, M Ruggiero, TP Fleming, PP Di Fiore, JS Greenberger, L Varticovski, J Schlessinger, G Rovera, and SA Aaronson

Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.

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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mutational Activation of ErbB2 Reveals a New Protein Kinase Autoinhibition Mechanism.
Y.-X. Fan, L. Wong, J. Ding, N. A. Spiridonov, R. C. Johnson, and G. R. Johnson (2008)
J. Biol. Chem. 283, 1588-1596
   Abstract »    Full Text »    PDF »
Epidermal Growth Factor Receptor (EGFR) Antibody Down-regulates Mutant Receptors and Inhibits Tumors Expressing EGFR Mutations.
M. Perez-Torres, M. Guix, A. Gonzalez, and C. L. Arteaga (2006)
J. Biol. Chem. 281, 40183-40192
   Abstract »    Full Text »    PDF »
Association with HSP90 Inhibits Cbl-Mediated Down-regulation of Mutant Epidermal Growth Factor Receptors..
S. Yang, S. Qu, M. Perez-Tores, A. Sawai, N. Rosen, D. B. Solit, and C. L. Arteaga (2006)
Cancer Res. 66, 6990-6997
   Abstract »    Full Text »    PDF »
Proteolytic Cleavage and Phosphorylation of a Tumor-associated ErbB4 Isoform Promote Ligand-independent Survival and Cancer Cell Growth.
J. A. Maatta, M. Sundvall, T. T. Junttila, L. Peri, V. J. O. Laine, J. Isola, M. Egeblad, and K. Elenius (2006)
Mol. Biol. Cell 17, 67-79
   Abstract »    Full Text »    PDF »
Angiopoietin-regulated recruitment of vascular smooth muscle cells by endothelial-derived heparin binding EGF-like growth factor.
E. IIVANAINEN, L. NELIMARKKA, V. ELENIUS, S.-M. HEIKKINEN, T. T. JUNTTILA, L. SIHOMBING, M. SUNDVALL, J. A. MAATTA, V. J. O. LAINE, S. YLA-HERTTUALA, et al. (2003)
FASEB J 17, 1609-1621
   Abstract »    Full Text »    PDF »
Activity of the farnesyl protein transferase inhibitor SCH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia.
D. G. Peters, R. R. Hoover, M. J. Gerlach, E. Y. Koh, H. Zhang, K. Choe, P. Kirschmeier, W. R. Bishop, and G. Q. Daley (2001)
Blood 97, 1404-1412
   Abstract »    Full Text »    PDF »
Epidermal Growth Factor Receptor vIII Enhances Tumorigenicity in Human Breast Cancer.
C. K. Tang, X.-Q. Gong, D. K. Moscatello, A. J. Wong, and M. E. Lippman (2000)
Cancer Res. 60, 3081-3087
   Abstract »    Full Text »    PDF »
Cyclic Nucleotide Phosphodiesterase 3B Is a Downstream Target of Protein Kinase B and May Be Involved in Regulation of Effects of Protein Kinase B on Thymidine Incorporation in FDCP2 Cells.
F. Ahmad, L.-N. Cong, L. Stenson Holst, L.-M. Wang, T. Rahn Landstrom, J. H. Pierce, M. J. Quon, E. Degerman, and V. C. Manganiello (2000)
J. Immunol. 164, 4678-4688
   Abstract »    Full Text »    PDF »
Multiple Growth Factor Induction of a Murine Early Response Gene That Complements a Lethal Defect in Yeast Ribosome Biogenesis.
S. A. Nelson, J. P. Aris, B. K. R. Patel, and W. J. LaRochelle (2000)
J. Biol. Chem. 275, 13835-13841
   Abstract »    Full Text »    PDF »
The Tetraspanin CD9 Associates with Transmembrane TGF-{alpha} and Regulates TGF-{alpha}-induced EGF Receptor Activation and Cell Proliferation.
W. Shi, H. Fan, L. Shum, and R. Derynck (2000)
J. Cell Biol. 148, 591-602
   Abstract »    Full Text »    PDF »
Inverse Relationship between Epidermal Growth Factor Receptor Expression and Radiocurability of Murine Carcinomas.
T. Akimoto, N. R. Hunter, L. Buchmiller, K. Mason, K. K. Ang, and L. Milas (1999)
Clin. Cancer Res. 5, 2884-2890
   Abstract »    Full Text »    PDF »
Contact-dependent Growth Inhibition and Apoptosis of Epidermal Growth Factor (EGF) Receptor-expressing Cells by the Membrane-anchored Form of Heparin-binding EGF-like Growth Factor.
R. Iwamoto, K. Handa, and E. Mekada (1999)
J. Biol. Chem. 274, 25906-25912
   Abstract »    Full Text »    PDF »
Differential Roles of Akt, Rac, and Ral in R-Ras-Mediated Cellular Transformation, Adhesion, and Survival.
M. Osada, T. Tolkacheva, W. Li, T. O. Chan, P. N. Tsichlis, R. Saez, A. C. Kimmelman, and A. M.-L. Chan (1999)
Mol. Cell. Biol. 19, 6333-6344
   Abstract »    Full Text »    PDF »
IL-3 and IL-4 Activate Cyclic Nucleotide Phosphodiesterases 3 (PDE3) and 4 (PDE4) by Different Mechanisms in FDCP2 Myeloid Cells.
F. Ahmad, G. Gao, L. M. Wang, T. R. Landstrom, E. Degerman, J. H. Pierce, and V. C. Manganiello (1999)
J. Immunol. 162, 4864-4875
   Abstract »    Full Text »    PDF »
A Differential Requirement for the COOH-terminal Region of the Epidermal Growth Factor (EGF) Receptor in Amphiregulin and EGF Mitogenic Signaling.
L. Wong, T. B. Deb, S. A. Thompson, A. Wells, and G. R. Johnson (1999)
J. Biol. Chem. 274, 8900-8909
   Abstract »    Full Text »    PDF »
ErbB Tyrosine Kinases and the Two Neuregulin Families Constitute a Ligand-Receptor Network.
R. Pinkas-Kramarski, M. Shelly, B. C. Guarino, L. M. Wang, L. Lyass, I. Alroy, M. Alamandi, A. Kuo, J. D. Moyer, S. Lavi, et al. (1998)
Mol. Cell. Biol. 18, 6090-6101
   Abstract »    Full Text »
ErbB2 expression increases the spectrum and potency of ligand-mediated signal transduction through ErbB4.
L.-M. Wang, A. Kuo, M. Alimandi, M. C. Veri, C.-C. Lee, V. Kapoor, N. Ellmore, X.-H. Chen, and J. H. Pierce (1998)
PNAS 95, 6809-6814
   Abstract »    Full Text »    PDF »
Epiregulin Is a Potent Pan-ErbB Ligand That Preferentially Activates Heterodimeric Receptor Complexes.
M. Shelly, R. Pinkas-Kramarski, B. C. Guarino, H. Waterman, L.-M. Wang, L. Lyass, M. Alimandi, A. Kuo, S. S. Bacus, J. H. Pierce, et al. (1998)
J. Biol. Chem. 273, 10496-10505
   Abstract »    Full Text »    PDF »
Regulation of Bcl-xL expression in human keratinocytes by cell-substratum adhesion and the epidermal growth factor receptor.
U. Rodeck, M. Jost, J. DuHadaway, C. Kari, P. J. Jensen, B. Risse, and D. L. Ewert (1997)
PNAS 94, 5067-5072
   Abstract »    Full Text »    PDF »
EGF-R dependent regulation of keratinocyte survival.
U Rodeck, M Jost, C Kari, D. Shih, R. Lavker, D. Ewert, and P. Jensen (1997)
J. Cell Sci. 110, 113-121
   Abstract »    PDF »
Amino-terminal Processing of Cell Surface Heparin-binding Epidermal Growth Factor-like Growth Factor Up-regulates Its Juxtacrine but Not Its Paracrine Growth Factor Activity.
T. Nakagawa, S. Higashiyama, T. Mitamura, E. Mekada, and N. Taniguchi (1996)
J. Biol. Chem. 271, 30858-30863
   Abstract »    Full Text »    PDF »
An Epidermal Growth Factor Receptor/Jak2 Tyrosine Kinase Domain Chimera Induces Tyrosine Phosphorylation of Stat5 and Transduces a Growth Signal in Hematopoietic Cells.
N. Nakamura, H. Chin, N. Miyasaka, and O. Miura (1996)
J. Biol. Chem. 271, 19483-19488
   Abstract »    Full Text »    PDF »
HER4-mediated Biological and Biochemical Properties in NIH 3T3 Cells.
B. D. Cohen, J. M. Green, L. Foy, and H. P. Fell (1996)
J. Biol. Chem. 271, 4813-4818
   Abstract »    Full Text »    PDF »
Mouse preimplantation blastocysts adhere to cells expressing the transmembrane form of heparin-binding EGF-like growth factor.
G Raab, K Kover, B. Paria, S. Dey, R. Ezzell, and M Klagsbrun (1996)
Development 122, 637-645
   Abstract »    PDF »
Characterization of a Protein Kinase C-[IMAGE] (PKC-[IMAGE]) ATP Binding Mutant.
W. Li, J.-C. Yu, D.-Y. Shin, and J. H. Pierce (1995)
J. Biol. Chem. 270, 8311-8318
   Abstract »    Full Text »    PDF »
Diphtheria Toxin Binds to the Epidermal Growth Factor (EGF)-like Domain of Human Heparin-binding EGF-like Growth Factor/Diphtheria Toxin Receptor and Inhibits Specifically Its Mitogenic Activity.
T. Mitamura, S. Higashiyama, N. Taniguchi, M. Klagsbrun, and E. Mekada (1995)
J. Biol. Chem. 270, 1015-1019
   Abstract »    Full Text »    PDF »
IRS-1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells.
L. Wang, M. Myers Jr, X. Sun, S. Aaronson, M White, and J. Pierce (1993)
Science 261, 1591-1594
   Abstract »    PDF »
Growth factors and cancer.
S. Aaronson (1991)
Science 254, 1146-1153
   Abstract »    PDF »
The human t(1;19) translocation in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with differing transforming potentials..
M P Kamps, A T Look, and D Baltimore (1991)
Genes & Dev. 5, 358-368
   Abstract »    PDF »
Expression cDNA cloning of the KGF receptor by creation of a transforming autocrine loop.
T Miki, T. Fleming, D. Bottaro, J. Rubin, D Ron, and S. Aaronson (1991)
Science 251, 72-75
   Abstract »    PDF »
EGF receptor and erbB-2 tyrosine kinase domains confer cell specificity for mitogenic signaling.
P. Di Fiore, O Segatto, W. Taylor, S. Aaronson, and J. Pierce (1990)
Science 248, 79-83
   Abstract »    PDF »
Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes.
T Matsui, M Heidaran, T Miki, N Popescu, W La Rochelle, M Kraus, J Pierce, and S Aaronson (1989)
Science 243, 800-804
   Abstract »    PDF »
Overexpression of transforming growth factor alpha in psoriatic epidermis.
J. Elder, G. Fisher, P. Lindquist, G. Bennett, M. Pittelkow, R. Coffey Jr, L Ellingsworth, R Derynck, and J. Voorhees (1989)
Science 243, 811-814
   Abstract »    PDF »
Antiphosphotyrosine recovery of phospholipase C activity after EGF treatment of A-431 cells.
M. Wahl, T. Daniel, and G Carpenter (1988)
Science 241, 968-970
   Abstract »    PDF »
Identification of Anaplastic Lymphoma Kinase as a Receptor for the Growth Factor Pleiotrophin.
G. E. Stoica, A. Kuo, A. Aigner, I. Sunitha, B. Souttou, C. Malerczyk, D. J. Caughey, D. Wen, A. Karavanov, A. T. Riegel, et al. (2001)
J. Biol. Chem. 276, 16772-16779
   Abstract »    Full Text »    PDF »
Epidermal Growth Factor (EGF) Receptor Kinase-independent Signaling by EGF.
T. B. Deb, L. Su, L. Wong, E. Bonvini, A. Wells, M. David, and G. R. Johnson (2001)
J. Biol. Chem. 276, 15554-15560
   Abstract »    Full Text »    PDF »
Dissociation of Heparan Sulfate and Receptor Binding Domains of Hepatocyte Growth Factor Reveals That Heparan Sulfate-c-Met Interaction Facilitates Signaling.
J. S. Rubin, R. M. Day, D. Breckenridge, N. Atabey, W. G. Taylor, S. J. Stahl, P. T. Wingfield, J. D. Kaufman, R. Schwall, and D. P. Bottaro (2001)
J. Biol. Chem. 276, 32977-32983
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)