The discovery of receptor tyrosine kinases: targets for cancer therapy

Receptor tyrosine kinases are a subclass of cell-surface growth-factor receptors with an intrinsic, ligand-controlled tyrosine-kinase activity. They regulate diverse functions in normal cells and have a crucial role in oncogenesis. Twenty years ago, the first primary structure of a receptor tyrosine kinase, the epidermal growth factor receptor, was elucidated. The characterization of both the molecular architecture of receptor tyrosine kinases and the main functions of these proteins and their ligands in tumorigenesis opened the door to a new era in molecular oncology and paved the way to the development of the first target-specific cancer therapeutics.

[1]  A. Riggs,et al.  Expression in Escherichia coli of a chemically synthesized gene for the hormone somatostatin. , 1977, Science.

[2]  N. Hynes,et al.  ErbB‐2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling , 1997, The EMBO journal.

[3]  W Godolphin,et al.  Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. , 1989, Science.

[4]  Andrius Kazlauskas,et al.  The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase , 1995, Cell.

[5]  A. Ullrich,et al.  Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences , 1984, Nature.

[6]  Jonathan A. Cooper,et al.  Epidermal growth factor induces rapid tyrosine phosphorylation of proteins in A431 human tumor cells , 1981, Cell.

[7]  H Ueno,et al.  The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. , 1992, Science.

[8]  David C. Lee,et al.  An essential role for ectodomain shedding in mammalian development. , 1998, Science.

[9]  P. N. Rao,et al.  Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification , 2001, Science.

[10]  A. Ullrich,et al.  A mutant epidermal growth factor receptor with defective protein tyrosine kinase is unable to stimulate proto-oncogene expression and DNA synthesis , 1987, Molecular and cellular biology.

[11]  G. Frantz,et al.  ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice. , 1997, Development.

[12]  A. Kaye,et al.  Selective amplification of the cytoplasmic domain of the epidermal growth factor receptor gene in glioblastoma multiforme. , 1988, Cancer research.

[13]  W. McGuire,et al.  Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. , 1987, Science.

[14]  P. H. Seeburg,et al.  Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes , 1985, Nature.

[15]  Edouard C. Nice,et al.  Crystal Structure of a Truncated Epidermal Growth Factor Receptor Extracellular Domain Bound to Transforming Growth Factor α , 2002, Cell.

[16]  P. Seeburg,et al.  The c‐sis gene encodes a precursor of the B chain of platelet‐derived growth factor. , 1984, The EMBO journal.

[17]  A. Ullrich,et al.  Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant , 1994, Nature.

[18]  H. Kung,et al.  Activated type I phosphatidylinositol kinase is associated with the epidermal growth factor (EGF) receptor following EGF stimulation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Stefan Hart,et al.  TACE cleavage of proamphiregulin regulates GPCR‐induced proliferation and motility of cancer cells , 2003, The EMBO journal.

[20]  A. Ullrich,et al.  Point mutation at the ATP binding site of EGF receptor abolishes protein-tyrosine kinase activity and alters cellular routing , 1987, Cell.

[21]  Mark R. Smith,et al.  Requirement for c-ras proteins during viral oncogene transformation , 1986, Nature.

[22]  T. Hunter,et al.  Transforming gene product of Rous sarcoma virus phosphorylates tyrosine , 1980, Proceedings of the National Academy of Sciences.

[23]  Leonard,et al.  Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. , 1997, Cancer research.

[24]  F. Shibasaki,et al.  Ash/Grb‐2, a SH2/SH3‐containing protein, couples to signaling for mitogenesis and cytoskeletal reorganization by EGF and PDGF. , 1993, The EMBO journal.

[25]  A. Ullrich,et al.  Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo. , 1996, Cancer research.

[26]  C. Marshall,et al.  Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation , 1995, Cell.

[27]  S. Cohen,et al.  The stimulation of epidermal proliferation by a specific protein (EGF). , 1965, Developmental biology.

[28]  A. Ullrich,et al.  Insulin-like growth factor II precursor gene organization in relation to insulin gene family , 1984, Nature.

[29]  A. Ullrich,et al.  A chimaeric receptor allows insulin to stimulate tyrosine kinase activity of epidermal growth factor receptor , 1986, Nature.

[30]  R. Weinberg,et al.  The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen , 1984, Nature.

[31]  C Collins,et al.  Insulin‐like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. , 1986, The EMBO journal.

[32]  A. Ullrich,et al.  Human proto‐oncogene c‐kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. , 1987, The EMBO journal.

[33]  A. Ullrich,et al.  The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling , 1992, Cell.

[34]  A. Ullrich,et al.  Characterization of murine monoclonal antibodies reactive to either the human epidermal growth factor receptor or HER2/neu gene product. , 1990, Cancer research.

[35]  Kenneth J. Hillan,et al.  Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene , 1996, Nature.

[36]  R. Weinberg,et al.  Identification of a nucleotide exchange-promoting activity for p21ras. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Martin R. Schneider,et al.  PTK 787 / ZK 222584 , a Novel and Potent Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases , Impairs Vascular Endothelial Growth Factor-induced Responses and Tumor Growth after Oral Administration , 2000 .

[38]  A. Ullrich,et al.  Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor , 1983, Nature.

[39]  P. Seeburg,et al.  Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells , 1984, Nature.

[40]  A. Ullrich,et al.  SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. , 1999, Cancer research.

[41]  T Pawson,et al.  Src homology region 2 domains direct protein-protein interactions in signal transduction. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[42]  J. Martial,et al.  Human growth hormone: complementary DNA cloning and expression in bacteria. , 1979, Science.

[43]  S. Cohen,et al.  Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes. , 1980, The Journal of biological chemistry.

[44]  E. Chen,et al.  Human transforming growth factor-α: Precursor structure and expression in E. coli , 1984, Cell.

[45]  W. Rutter,et al.  Rat insulin genes: construction of plasmids containing the coding sequences. , 1977, Science.

[46]  R. Levi‐montalcini EFFECTS OF MOUSE TUMOR TRANSPLANTATION ON THE NERVOUS SYSTEM , 1952, Annals of the New York Academy of Sciences.

[47]  K. Herrup,et al.  Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. , 1995, Science.

[48]  G. Carpenter,et al.  Epidermal growth factor stimulates phosphorylation in membrane preparations in vitro , 1978, Nature.

[49]  C R King,et al.  Amplification of a novel v-erbB-related gene in a human mammary carcinoma. , 1985, Science.

[50]  J. Schlessinger,et al.  Ligand-independent tyrosine phosphorylation of EGF receptor and the erbB-2/neu proto-oncogene product is induced by hyperosmotic shock. , 1989, Oncogene.

[51]  Giovanni Parmigiani,et al.  Mutational Analysis of the Tyrosine Kinome in Colorectal Cancers , 2003, Nature Reviews Cancer.

[52]  R. Peek,et al.  cag+ Helicobacter pylori Induce Transactivation of the Epidermal Growth Factor Receptor in AGS Gastric Epithelial Cells* , 2001, The Journal of Biological Chemistry.

[53]  Inder M. Verma,et al.  Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus , 1986, Nature.

[54]  A. Ullrich,et al.  p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor , 1989, Molecular and cellular biology.

[55]  J. Mestan,et al.  PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. , 2000, Cancer research.

[56]  A. Wolfman,et al.  A cytosolic protein catalyzes the release of GDP from p21ras. , 1990, Science.

[57]  Jae-Hoon Kim,et al.  Crystal Structure of the Complex of Human Epidermal Growth Factor and Receptor Extracellular Domains , 2002, Cell.

[58]  P. Seeburg,et al.  Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. , 1985, Science.

[59]  J. Folkman Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.

[60]  F. McCormick How receptors turn Ras on , 1993, Nature.

[61]  Philippe Shubik,et al.  VEGF and the quest for tumour angiogenesis factors , 2022 .

[62]  L. Silengo,et al.  Integrins induce activation of EGF receptor: role in MAP kinase induction and adhesion‐dependent cell survival , 1998, The EMBO journal.

[63]  D. Tuveson,et al.  Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. , 2001, The New England journal of medicine.

[64]  David C. Lee,et al.  Defective valvulogenesis in HB‐EGF and TACE‐null mice is associated with aberrant BMP signaling , 2003, The EMBO journal.

[65]  A. Burgess,et al.  Anti-sense transforming growth factor alpha oligonucleotides inhibit autocrine stimulated proliferation of a colon carcinoma cell line. , 1992, Molecular biology of the cell.

[66]  Z. Kam,et al.  c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor. , 1998, Genes & development.

[67]  H. Hihara,et al.  A new avian erythroblastosis virus, AEV-H, carries erbB gene responsible for the induction of both erythroblastosis and sarcomas , 1983, Cell.

[68]  J. Mendelsohn,et al.  Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. , 1983, Molecular biology & medicine.

[69]  Hiroshi Asanuma,et al.  Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: Metalloproteinase inhibitors as a new therapy , 2002, Nature Medicine.

[70]  J. Schlessinger,et al.  Signal transduction by allosteric receptor oligomerization. , 1988, Trends in biochemical sciences.

[71]  P. Humphrey,et al.  Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[72]  C. Kahn,et al.  Insulin stimulates tyrosine phosphorylation of the insulin receptor in a cell-free system , 1982, Nature.

[73]  T. Hunter,et al.  An activity phosphorylating tyrosine in polyoma T antigen immunoprecipitates , 1979, Cell.

[74]  B. Mayer,et al.  Binding of transforming protein, P47gag-crk, to a broad range of phosphotyrosine-containing proteins. , 1990, Science.

[75]  J Folkman,et al.  Transplacental carcinogenesis by stilbestrol. , 1971, The New England journal of medicine.

[76]  D. Dimitrov,et al.  Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. , 1992, Biochemical and biophysical research communications.

[77]  J. Woodburn,et al.  Specific inhibition of epidermal growth factor receptor tyrosine kinase by 4-anilinoquinazolines , 2005, Breast Cancer Research and Treatment.

[78]  Janet Rossant,et al.  Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice , 1995, Nature.

[79]  G. Carpenter,et al.  Characterization of the binding of 125-I-labeled epidermal growth factor to human fibroblasts. , 1975, The Journal of biological chemistry.

[80]  Morag Park,et al.  Escape from Cbl-mediated downregulation: a recurrent theme for oncogenic deregulation of receptor tyrosine kinases. , 2003, Cancer cell.

[81]  T. Takenawa,et al.  Cloning of ASH, a ubiquitous protein composed of one Src homology region (SH) 2 and two SH3 domains, from human and rat cDNA libraries. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[82]  T. Hunter,et al.  Phospholipase C-γ is a substrate for the PDGF and EGF receptor protein-tyrosine kinases in vivo and in vitro , 1989, Cell.

[83]  Bing Li,et al.  Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo , 1993, Nature.

[84]  J. Mendelsohn,et al.  Growth stimulation of A431 cells by epidermal growth factor: identification of high-affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[85]  A. Levitzki,et al.  Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors , 1988, Science.

[86]  S. Cohen,et al.  Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. , 1962, The Journal of biological chemistry.

[87]  S. Cohen,et al.  Purification and properties of a nerve growth-promoting factor isolated from mouse sarcoma 180. , 1957, Cancer research.

[88]  R. Derynck,et al.  Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor , 1995, Nature.

[89]  Charles Eigenbrot,et al.  Crystal Structure at 1.7 Å Resolution of VEGF in Complex with Domain 2 of the Flt-1 Receptor , 1997, Cell.

[90]  A. Ullrich,et al.  Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors , 1996, Nature.

[91]  Kohjiro Ueki,et al.  Tyrosine phosphorylation of the EGF receptor by the kinase Jak2 is induced by growth hormone , 1997, Nature.

[92]  Nicole Nelson,et al.  A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells , 1997, Nature.

[93]  W. Langdon,et al.  Tyrosine kinase activity of the EGF receptor is enhanced by the expression of oncogenic 70Z-Cbl , 1997, Oncogene.

[94]  J. Darnell,et al.  Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. , 1994, Science.

[95]  R. Weinberg,et al.  Monoclonal antibodies identify a cell-surface antigen associated with an activated cellular oncogene , 1984, Nature.

[96]  A. Zilberstein,et al.  EGF induces tyrosine phosphorylation of phospholipase C-II: A potential mechanism for EGF receptor signaling , 1989, Cell.

[97]  B. Druker,et al.  Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. , 2000, The Journal of pharmacology and experimental therapeutics.

[98]  F. McCormick Signal transduction. How receptors turn Ras on. , 1993, Nature.

[99]  A. Bridges,et al.  A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. , 1994, Science.

[100]  A. Ullrich,et al.  Human β-nerve growth factor gene sequence highly homologous to that of mouse , 1983, Nature.

[101]  Christian Wiesmann,et al.  Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor , 1999, Nature.

[102]  J. Rossant,et al.  Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium , 1995, Nature.

[103]  Masatsugu Hori,et al.  Heparin-binding EGF-like growth factor and ErbB signaling is essential for heart function , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[104]  Philippe Soriano The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites. , 1997, Development.

[105]  Jürg Zimmermann,et al.  Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells , 1996, Nature Medicine.

[106]  T. Hunter,et al.  Oncogenic kinase signalling , 2001, Nature.

[107]  C. Heldin,et al.  Stimulation of tyrosine-specific phosphorylation by platelet-derived growth factor , 1982, Nature.

[108]  B. Curry,et al.  ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. , 2002, Cancer research.

[109]  Philippe Soriano,et al.  Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice. , 1994, Genes & development.

[110]  David C. Lee,et al.  TGFα deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice , 1993, Cell.

[111]  K. Jarnagin,et al.  The human insulin receptor cDNA: The structural basis for hormone-activated transmembrane signalling , 1985, Cell.

[112]  A. Ullrich,et al.  Critical Role of Calcium- dependent Epidermal Growth Factor Receptor Transactivation in PC12 Cell Membrane Depolarization and Bradykinin Signaling* , 1997, The Journal of Biological Chemistry.

[113]  C. Basbaum,et al.  Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells , 2002, Nature Medicine.

[114]  W. Rutter,et al.  Structure of a mouse submaxillary messenger RNA encoding epidermal growth factor and seven related proteins. , 1983, Science.

[115]  D. Engelman,et al.  Two EGF molecules contribute additively to stabilization of the EGFR dimer , 1997, The EMBO journal.

[116]  David C. Lee,et al.  Tumor Necrosis Factor-α Converting Enzyme (TACE) Regulates Epidermal Growth Factor Receptor Ligand Availability* , 2002, The Journal of Biological Chemistry.

[117]  Stanley N. Cohen,et al.  EFFECTS OF THE EXTRACT OF THE MOUSE SUBMAXILLARY SALIVARY GLANDS ON THE SYMPATHETIC SYSTEM OF MAMMALS * , 1960, Annals of the New York Academy of Sciences.

[118]  D. Stern,et al.  EGF‐stimulated tyrosine phosphorylation of p185neu: a potential model for receptor interactions. , 1988, The EMBO journal.

[119]  Brian Higgins,et al.  Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. , 2002, Cancer cell.

[120]  E. Nice,et al.  Mice with a null mutation of the TGFα gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation , 1993, Cell.

[121]  L. Ellis,et al.  Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis. , 1999, Cancer research.

[122]  David C. Lee,et al.  Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development. , 1999, Development.

[123]  E. Wagner,et al.  Anti-oncogenic activity of signalling-defective epidermal growth factor receptor mutants , 1992, Molecular and cellular biology.

[124]  A. Ullrich,et al.  EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF , 1999, Nature.

[125]  M. Heinrich,et al.  SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. , 2003, Blood.

[126]  J. Massagué TGF-beta signal transduction. , 1998, Annual review of biochemistry.

[127]  Rüdiger Klein,et al.  Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor , 1995, Nature.

[128]  A. Levitzki,et al.  Epidermal-growth-factor-dependent activation of the src-family kinases. , 1994, European journal of biochemistry.

[129]  E. Wagner,et al.  Strain-dependent epithelial defects in mice lacking the EGF receptor. , 1995, Science.

[130]  Lieve Moons,et al.  Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele , 1996, Nature.

[131]  J. Schlessinger,et al.  Egf binding to its receptor triggers a rapid tyrosine phosphorylation of the erbB‐2 protein in the mammary tumor cell line SK‐BR‐3. , 1988, The EMBO journal.

[132]  A. D. Van den Abbeele,et al.  Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[133]  J. Feramisco,et al.  Epidermal growth factor stimulates guanine nucleotide binding activity and phosphorylation of ras oncogene proteins , 1984, Nature.

[134]  Jonathan A. Cooper,et al.  Similar effects of platelet-derived growth factor and epidermal growth factor on the phosphorylation of tyrosine in cellular proteins , 1982, Cell.

[135]  A. Ullrich,et al.  Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors , 1986, Nature.

[136]  D. Goeddel,et al.  Nucleotide sequence of human preproinsulin complementary DNA. , 1980, Science.

[137]  T. Quinn,et al.  Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[138]  A. Ullrich,et al.  High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis , 1993, Cell.

[139]  D. Givol,et al.  Nucleotide sequence analysis identifies the human c-sis proto-oncogene as a structural gene for platelet-derived growth factor , 1984, Cell.

[140]  Kuo-Fen Lee,et al.  Requirement for neuregulin receptor erbB2 in neural and cardiac development , 1995, Nature.