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Breast Cancer Research
Published in: Breast Cancer Research 3/2000

01-06-2000 | Review

Tyrosine kinase signalling in breast cancer: Epidermal growth factor receptor - convergence point for signal integration and diversification

Authors: Norbert Prenzel, Esther Zwick, Michael Leserer, Axel Ullrich

Published in: Breast Cancer Research | Issue 3/2000

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Abstract

Cross-communication between different signalling systems is critical for the integration of multiple and changing environmental influences on individual cells. The epidermal growth factor receptor (EGFR) has been identified as a key element in the complex signalling network that is utilized by various classes of cell-surface receptors. This nonclassical mode of signalling system cross-talk, in distinction to receptor activation induced by cognate ligands, has been termed 'signal transactivation'. With the EGFR as the convergence point and distribution focus, this scenario may involve signals emitted by other members of the tyrosine kinase family, cytokine receptors, ion channels, G-protein-coupled receptors and integrins.
Literature
1.
Ullrich A, Coussens L, Hayflick JS, et al: Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature. 1984, 309: 418-425.CrossRefPubMed
2.
Alroy I, Yarden Y: The ErbB signaling network in embryogenesis and oncogenesis:signal diversification through combinatorial ligand-receptor interactions. FEBS Lett. 1997, 410: 83-86. 10.1016/S0014-5793(97)00412-2.CrossRefPubMed
3.
Riesell DJ, Stern DF: Specificity within the EGF family/ErbB receptor family signaling network. Bioessays. 1998, 20: 41-48. 10.1002/(SICI)1521-1878(199801)20:1<41::AID-BIES7>3.0.CO;2-V.CrossRef
4.
Van Agthoven T, Timmermans M, Dorssers LC, Henzen-Logmans SC: Expression of estrogen, progesterone and epidermal growth factor receptors in primary and metastatic breast cancer. Int J Cancer. 1995, 63: 790-793.CrossRefPubMed
5.
Earp HS, Dawson TL, Li X, Yu H: Heterodimerization and functional interaction between EGF receptor family members: a new signaling paradigm with implications for breast cancer research. Breast Cancer Res Treat. 1995, 35: 115-132.CrossRefPubMed
6.
Massagué J, Pandiella A: Membrane-anchored growth factors. Annu Rev Biochem. 1993, 62: 515-541. 10.1146/annurev.bi.62.070193.002503.CrossRefPubMed
7.
Schlessinger J, Ullrich A: Growth factor signaling by receptor tyrosine kinases. Neuron. 1992, 9: 383-391.CrossRefPubMed
8.
Hackel PO, Zwick E, Prenzel N, Ullrich A: Epidermal growth factor receptors: critical mediators of multiple receptor pathways. Curr Opin Cell Biol. 1999, 11: 184-189. 10.1016/S0955-0674(99)80024-6.CrossRefPubMed
9.
Luttrell LM, Daaka Y, Lefkowitz RJ: Regulation of tyrosine kinase cascades by G-protein-coupled receptors. Curr Opin Cell Biol. 1999, 11: 177-183. 10.1016/S0955-0674(99)80023-4.CrossRefPubMed
10.
Zwick E, Hackel PO, Prenzel N, Ullrich A: The EGF receptor as central transducer of heterologous signalling systems. Trends Pharmacol Sci. 1999, 20: 408-412. 10.1016/S0165-6147(99)01373-5.CrossRefPubMed
11.
Carpenter G: Employment of the epidermal growth factor receptor in growth factor-independent signaling pathways. J Cell Biol. 1999, 146: 697-702. 10.1083/jcb.146.4.697.CrossRefPubMedPubMedCentral
12.
Hamm HE: The many faces of G-protein signaling. J Biol Chem. 1998, 273: 669-672. 10.1074/jbc.273.2.669.CrossRefPubMed
13.
Dhanasekaran N, Tsim S-T, Dermott JM, Onesime D: Regulation of cell proliferation by G-proteins. Oncogene. 1998, 17: 1383-1394. 10.1038/sj.onc.1202242.CrossRefPubMed
14.
Xu N, Voyno-Yasenetskaya T, Gutkind S: Potent transforming activity of the G13 α subunit defines a novel family of oncogenes. Biochem Biophys Res Commun. 1994, 201: 603-609. 10.1006/bbrc.1994.1744.CrossRefPubMed
15.
Allen LF, Lefkowitz RJ, Caron MG, Cotecchia S: G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the α1B- adrenergic receptor enhances mitogenesis and tumorigenicity. Proc Natl Acad Sci USA. 1991, 88: 11354-11358.CrossRefPubMedPubMedCentral
16.
Lyons JL, Landis CA, Harsh G, et al: Two G protein oncogenes in human endocrine tumors. Science. 1990, 249: 655-659.CrossRefPubMed
17.
Parma J, Duprez L, Van Sande J, et al: Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature. 1993, 365: 649-651. 10.1038/365649a0.CrossRefPubMed
18.
Howe LR, Marshall CJ: Lysophosphatidic acid stimulates mitogenactivated protein kinase activation via a G-protein-coupled pathway requiring p21ras and p74raf-1. J Biol Chem. 1993, 268: 20717-20720.PubMed
19.
Crespo P, Xu N, Simonds WF, Gutkind S: Ras-dependent activation of MAP kinase pathway mediated by G-protein βγsubunits. Nature. 1994, 369: 418-420. 10.1038/369418a0.CrossRefPubMed
20.
Van Corven EJ, Hordijk PL, Medema RH, Bos JL, Moolenaar WH: Pertussis toxin-sensitive activation of p21ras by G-protein-coupled receptor agonists in fibroblasts. Proc Natl Acad Sci USA. 1993, 90: 1257-1261.CrossRefPubMedPubMedCentral
21.
Daub H, Weiss FU, Wallasch C, Ullrich A: Role of transactivation of the EGF receptor in signaling by G-protein-coupled receptors. Nature. 1996, 379: 557-560. 10.1038/379557a0.CrossRefPubMed
22.
Dikic J, Tokina G, Lev S, Courtneidge SA, Schlessinger J: A role for Pyk2 and Src in linking G-protein-coupled receptors win MAPkinase activation. Nature. 1996, 383: 547-550. 10.1038/383547a0.CrossRefPubMed
23.
Luttrell LM, Hawes BE, van Biesen T, et al: Role of c-Src tyrosine kinase in G protein-coupled receptor-and Gβγsubunit mediated activation mitogen activated protein kinases. J Biol Chem. 1996, 271: 19443-19450. 10.1074/jbc.271.21.12133.CrossRefPubMed
24.
Daub H, Wallasch C, Lankenau A, Herrlich A, Ullrich A: Signal characteristics of G-protein-transactivated EGF receptor. EMBO J. 1997, 16: 101-113. 10.1093/emboj/16.23.7032.CrossRef
25.
Eguchi S, Numaguchi K, Iwasaki H, et al: Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J Biol Chem. 1998, 273: 8890-8896. 10.1074/jbc.273.15.8890.CrossRefPubMed
26.
Keely SJ, Uribe JM, Barrett KE: Carbachol stimulates transactivation of epidermal growth factor receptor and mitogen-activated protein kinase in T84 cells. J Biol Chem. 1998, 273: 27111-27117. 10.1074/jbc.273.42.27111.CrossRefPubMed
27.
Tsai W, Morielli AD, Peralta EG: The m1 muscarinic acetylcholine receptor transactivates the EGF receptor to modulate log channel activity. EMBO J. 1997, 16: 4597-4605. 10.1093/emboj/16.15.4597.CrossRefPubMedPubMedCentral
28.
Zwick E, Daub H, Aoki N, et al: Critical role of calcium-dependent epidermal growth factor receptor transactivation in PC12 cell membrane depolarization and bradykinin signaling. J Biol Chem. 1997, 272: 24767-24770. 10.1074/jbc.272.40.24767.CrossRefPubMed
29.
Cunnick JM, Dorsey JF, Standley J, et al: Role of tyrosine kinase activity of epidermal growth factor receptor in the lysophosphatidic acid-stimulated mitogen-activated protein kinase pathway. Biol Chem. 1998, 273: 14468-14475. 10.1074/jbc.273.23.14468.CrossRef
30.
Schwartzberg PL: The many faces of Src: multiple functions of a prototypical tyrosine kinase. Oncogene. 1998, 17: 1463-1468. 10.1038/sj.onc.1202176.CrossRefPubMed
31.
Luttrell LM, Della Rocca GJ, vanBiesen T, Luttrell DK, Lefkowitz RH: Gβγsubunits mediate Src-dependent phosphorylation of the epidermal growth factor receptor. J Biol Chem. 1997, 272: 4637-4644. 10.1074/jbc.272.50.31648.CrossRefPubMed
32.
Della Rocca GJ, Maudsley S, Daaka Y, Lefkowitz RJ, Luttrell LM: Pleiotropic coupling of G protein-coupled receptors to the mitogen-activated protein kinase cascade. J Biol Chem. 1999, 274: 13978-13984. 10.1074/jbc.274.20.13978.CrossRefPubMed
33.
Vaingankar SM, Martins-Green M: Thrombin activation of the 9E3/CEF4 chemokine involves tyrosine kinases including c-src and the epidermal growth factor receptor. J Biol Chem. 1998, 273: 5226-5234. 10.1074/jbc.273.9.5226.CrossRefPubMed
34.
Luttrell LM, Ferguson SSG, Daaka Y, et al: β-Arrestin-dependent formation of β2 adrenergic receptor-Src protein kinase complexes. Science. 1999, 283: 655-661. 10.1126/science.283.5402.655.CrossRefPubMed
35.
Stover DR, Becker M, Liebetanz J, Lydon NB: Src phosphorylation of the epidermal growth factor receptor at novel sites mediates receptor interaction with src and p85α. J Biol Chem. 1995, 270: 15591-15597. 10.1074/jbc.270.26.15591.CrossRefPubMed
36.
Biscardi JS, Maa M, Tice DA, et al: C-Src-mediated phosphorylation of the epidermal growth factor receptor on Tyr845 and Tyr1101 is associated with modulation of receptor function. J Biol Chem. 1999, 274: 8335-8344. 10.1074/jbc.274.12.8335.CrossRefPubMed
37.
Tice DA, Biscardi JS, Nickles AL, Parson SJ: Mechanism of biological synergy between cellular Src and epidermal growth factor receptor. Proc Natl Acad Sci USA. 1999, 96: 1415-1420. 10.1073/pnas.96.4.1415.CrossRefPubMedPubMedCentral
38.
Luttrell DK, Lee A, Lansing TJ, et al: Involvement of pp60c-src with two major signaling pathways in human breast cancer. Proc Natl Acad Sci USA. 1994, 91: 83-87.CrossRefPubMedPubMedCentral
39.
Soltoff SP: Related adhesion focal tyrosine kinase and the epidermal growth factor receptor mediate the stimulation of mitogen-activated protein kinase by the G-protein-coupled P2Y2 receptor. J Biol Chem. 1998, 273: 23110-23117. 10.1074/jbc.273.36.23110.CrossRefPubMed
40.
Adomeit A, Graness A, Gross S, et al: Bradykinin B2 receptor-mediated mitogen-activated protein kinase activation in COS-7 cells requires dual signaling via both protein kinase C pathway and epidermal growth factor receptor transactivation. Mol Cell Biol. 1999, 19: 5289-5297.CrossRefPubMedPubMedCentral
41.
Rosen LB, Greenberg ME: Stimulation of growth factor receptor signal transduction by activation of voltage-sensitive calcium channels. Proc Natl Acad Sci USA. 1996, 93: 1113-1118. 10.1073/pnas.93.3.1113.CrossRefPubMedPubMedCentral
42.
Murasawa S, Mori Y, Nozawa Y, et al: Angiotensin II type 1 receptor induced extracellular signal-regulated protein kinase activation is mediated by Ca2+/calmodulin dependent transactivation of epidermal growth factor receptor. Circ Res. 1998, 82: 1338-1348.CrossRefPubMed
43.
Lev S, Moreno H, Martinez R, et al: Protein tyrosine kinase PYK2 involved in Ca(2+) induced regulation of ion channel and MAP kinase functions. Nature. 1995, 376: 737-745. 10.1038/376737a0.CrossRefPubMed
44.
Zwick E, Wallasch C, Daub H, Ullrich A: Distinct calcium-dependent pathways of epidermal growth factor receptor transactivation and PYK2 tyrosine phosphorylation in PC12 cells. J Biol Chem. 1999, 274: 20989-20996. 10.1074/jbc.274.30.20989.CrossRefPubMed
45.
Lopez-llasaca M, Crespo P, Pellici PG, Gutkind JS, Wetzker R: Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI3-kinase γ. Science. 1997, 275: 394-397. 10.1126/science.275.5298.394.CrossRef
46.
Hu Z-W, Shi X-Y, Lin RZ, Hoffman BB: α1 adrenergic receptors activate phosphatidylinositol 3-kinase in human vascular smooth muscle cells. J Biol Chem. 1996, 271: 8977-8982. 10.1074/jbc.271.15.8977.CrossRefPubMed
47.
Hawes BE, Luttrell LM, van Biesen T, Lefkowitz RJ: Phosphatidylinositol 3-kinase is an early intermediate in the Gβγ-mediated mitogen-activated protein kinase signaling pathway. J Biol Chem. 1996, 271: 12133-12136. 10.1074/jbc.271.21.12133.CrossRefPubMed
48.
Laffargue M, Raynal P, Yart A, et al: An epidermal growth factor receptor/Gab1 signaling pathway is required for activation of phopshoinositide 3-kinase by lysophosphatidic acid. J Biol Chem. 1999, 274: 32835-32841. 10.1074/jbc.274.46.32835.CrossRefPubMed
49.
Iwasaki H, Eguchi S, Ueno H, Marumo F, Hirata Y: Endothelin-mediated vascular growth requires p42/p44 mitogen-activated protein kinase and p70 S6 kinase cascades via transactivation of epidermal growth factor receptor. Endocrinology. 1999, 140: 4659-4668. 10.1210/en.140.10.4659.PubMed
50.
Gohla A, Harhammer R, Schultz G: The G-protein G13 but not G12 mediates signalling from lysophosphatidic acid receptor via epidermal growth factor receptor to rho. J Biol Chem. 1998, 273: 4653-4659. 10.1074/jbc.273.8.4653.CrossRefPubMed
51.
Gohla A, Offermanns S, Wilkie TM, Schultz G: Differential involvement of Gα12 and Gα13 in receptor-mediated stress fiber formation. J Biol Chem. 1999, 274: 17901-17907. 10.1074/jbc.274.25.17901.CrossRefPubMed
52.
Prenzel N, Zwick E, Daub H, et al: EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature. 1999, 402: 884-888. 10.1038/47260.PubMed
53.
Yamauchi T, Ueki K, Tobe K, et al: Tyrosine phosphorylation of the EGF receptor by the kinase Jak2 is induced by growth hormone. Nature. 1997, 390: 91-96. 10.1038/36369.CrossRefPubMed
54.
Qiu Y, Ravi L, Kung HJ: Requirement of ErbB2 for signaling by interleukin-6 in prostate carcinoma cells. Nature. 1998, 393: 83-85. 10.1038/30012.CrossRefPubMed
55.
Giancotti FG, Ruoslahti E: Integrin signaling. Science. 1999, 285: 1028-1032. 10.1126/science.285.5430.1028.CrossRefPubMed
56.
Moro L, Venturino M, Bozzo C, et al: Integrins Induce activation of EGF receptor: role in MAP kinase induction and adhesion-dependent cell survival. EMBO J. 1998, 17: 6622-6632. 10.1093/emboj/17.22.6622.CrossRefPubMedPubMedCentral
57.
Liu P, Anderson RGW: Spatial organization of EGF receptor transmodulation by PDGF. Biochem Biophys Res Commun. 1999, 261: 695-700. 10.1006/bbrc.1999.1082.CrossRefPubMed
58.
Habib AA, Högnason T, Stefansson K, Ratan RR: The epidermal growth factor receptor associates with and recruits phosphatidylinositol 3-kinase to the platelet-derived growth factor βreceptor. J Biol Chem. 1998, 273: 6885-6891. 10.1074/jbc.273.12.6885.CrossRefPubMed
59.
Seedorf K, Shearman M, Ullrich A: Rapid and long term effects of protein kinase C on receptor tyrosine kinase phosphorylation and degradation. J Biol Chem. 1995, 270: 18953-18960. 10.1074/jbc.270.32.18953.CrossRefPubMed
60.
Bagowski CP, Stein-Gerlach M, Choidas A, Ullrich A: Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor. EMBO J. 1999, 18: 5567-5576. 10.1093/emboj/18.20.5567.CrossRefPubMedPubMedCentral
Metadata
Title
Tyrosine kinase signalling in breast cancer: Epidermal growth factor receptor - convergence point for signal integration and diversification
Authors
Norbert Prenzel
Esther Zwick
Michael Leserer
Axel Ullrich
Publication date
01-06-2000
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2000
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr52

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