Home LiteratureArticle Details
PMID: 8026468 Published · ppublish English Journal Article

Identification of c-erbB-3 binding sites for phosphatidylinositol 3'-kinase and SHC using an EGF receptor/c-erbB-3 chimera.

The EMBO journal ·Vol. 13 ·No. 12 ·1994-06-15 ·Pages 2831-41

Prigent SA, Gullick WJ

Abstract

c-erbB-3 is a member of the type I (EGF receptor-related) family of growth factor receptors for which no ligand has been identified. To facilitate ligand stimulation we have constructed a chimeric receptor which possesses an activatable kinase and promotes the growth of NIH 3T3 fibroblasts. In this study we have shown that SHC and phosphatidylinositol 3'-kinase bind to the activated EGF receptor/c-erbB-3 chimera. Whereas p85 is not phosphorylated to a significant extent, SHC appears to be a major substrate for phosphorylation on tyrosine. In contrast to EGF receptor and c-erbB-2, we were unable to detect binding of activated c-erbB-3 to GRB2. Using synthetic peptides corresponding to each of 13 potential phosphorylation sites on c-erbB-3, we have shown that tyrosine 1309 is responsible for SHC binding. Peptides containing the motif YXXM inhibit p85 association. By comparison with recently reported SHC binding sites on Middle T antigen and Trk we have identified a SHC binding motif, NPXY.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Avian Proteins Base Sequence Cell Adhesion Cells, Cultured Cytoskeletal Proteins/metabolism ErbB Receptors/genetics,metabolism GRB2 Adaptor Protein Glutathione Transferase/genetics,metabolism Molecular Sequence Data Phosphatidylinositol 3-Kinases Phosphopeptides/genetics Phosphoproteins/metabolism Phosphorylation Phosphotransferases (Alcohol Group Acceptor)/metabolism Protein Binding Proteins/genetics,metabolism Proto-Oncogene Proteins/genetics,metabolism Recombinant Fusion Proteins/metabolism Second Messenger Systems
Chemicals
Adaptor Proteins, Signal Transducing Avian Proteins Cytoskeletal Proteins GRB2 Adaptor Protein Phosphopeptides Phosphoproteins Proteins Proto-Oncogene Proteins Recombinant Fusion Proteins cytoskeletal p85 protein, chicken Glutathione Transferase Phosphatidylinositol 3-Kinases Phosphotransferases (Alcohol Group Acceptor) ErbB Receptors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Prigent S A
Molecular Oncology Laboratory, Hammersmith Hospital, London, UK.
Gullick W J
References (69)
69 references, click to expand
  1. Epidermal growth factor. Relationship between receptor regulation and mitogenesis in 3T3 cells.
    J Biol Chem. 1978 Jun 10;253(11):3970-7 PMID: 306388
  2. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling.
    Cell. 1992 Aug 7;70(3):431-42 PMID: 1322798
  3. Expression of the c-erbB-2 protein in normal and transformed cells.
    Int J Cancer. 1987 Aug 15;40(2):246-54 PMID: 3301694
  4. Shc proteins are phosphorylated and regulated by the v-Src and v-Fps protein-tyrosine kinases.
    Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8869-73 PMID: 1409579
  5. Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling.
    Nature. 1993 May 6;363(6424):85-8 PMID: 8479541
  6. Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers.
    Br Med Bull. 1991 Jan;47(1):87-98 PMID: 1863851
  7. Grb2 mediates the EGF-dependent activation of guanine nucleotide exchange on Ras.
    Nature. 1993 May 6;363(6424):88-92 PMID: 8386805
  8. A chimaeric receptor allows insulin to stimulate tyrosine kinase activity of epidermal growth factor receptor.
    Nature. 1986 Nov 6-12;324(6092):68-70 PMID: 3024008
  9. erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells.
    Science. 1987 Jul 10;237(4811):178-82 PMID: 2885917
  10. Molecular cloning of the mouse grb2 gene: differential interaction of the Grb2 adaptor protein with epidermal growth factor and nerve growth factor receptors.
    Mol Cell Biol. 1993 Sep;13(9):5500-12 PMID: 7689150
  11. Antibodies to the autophosphorylation sites of the epidermal growth factor receptor protein-tyrosine kinase as probes of structure and function.
    EMBO J. 1985 Nov;4(11):2869-77 PMID: 2415353
  12. Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation.
    Science. 1993 Mar 12;259(5101):1611-4 PMID: 7681217
  13. Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.
    Science. 1993 May 28;260(5112):1338-43 PMID: 8493579
  14. Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells.
    J Virol. 1969 Nov;4(5):549-53 PMID: 4311790
  15. Enhancement of epidermal growth factor (EGF) and insulin-stimulated tyrosine phosphorylation of endogenous substrates by sodium selenate.
    FEBS Lett. 1992 Aug 10;308(1):38-42 PMID: 1644202
  16. Purification and characterization of bovine brain type I phosphatidylinositol kinase.
    Eur J Biochem. 1990 Aug 17;191(3):761-7 PMID: 2167854
  17. Heterodimerization of the erbB-1 and erbB-2 receptors in human breast carcinoma cells: a mechanism for receptor transregulation.
    Biochemistry. 1990 Dec 18;29(50):11024-8 PMID: 1980216
  18. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa.
    Anal Biochem. 1987 Nov 1;166(2):368-79 PMID: 2449095
  19. Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor.
    Cell. 1993 May 7;73(3):611-20 PMID: 8490966
  20. Phospholipase C-gamma 1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor's mitogenic signal.
    Cell. 1993 Apr 23;73(2):321-34 PMID: 7682895
  21. Demonstration of ligand-dependent signaling by the erbB-3 tyrosine kinase and its constitutive activation in human breast tumor cells.
    Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2900-4 PMID: 8464905
  22. SH3 domains direct cellular localization of signaling molecules.
    Cell. 1993 Jul 16;74(1):83-91 PMID: 8334708
  23. Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells.
    Cell. 1987 Dec 24;51(6):1063-70 PMID: 3500791
  24. The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1.
    Nature. 1993 May 6;363(6424):83-5 PMID: 8479540
  25. A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases.
    Nature. 1991 Aug 22;352(6337):736-9 PMID: 1652101
  26. Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells.
    Mol Cell Biol. 1991 Feb;11(2):979-86 PMID: 1671297
  27. Mutational analysis of a phosphotransfer motif essential for v-fps tyrosine kinase activity.
    Oncogene. 1988 Dec;3(6):665-72 PMID: 2577868
  28. Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew.
    Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11239-43 PMID: 1280823
  29. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation.
    Nature. 1985 May 16-22;315(6016):239-42 PMID: 2987699
  30. In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors.
    J Natl Cancer Inst. 1973 Nov;51(5):1417-23 PMID: 4357758
  31. Analysis of platelet-derived growth factor receptor domain function using a novel chimeric receptor approach.
    J Biol Chem. 1991 Jul 5;266(19):12424-31 PMID: 1648098
  32. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.
    Science. 1988 Jul 1;241(4861):42-52 PMID: 3291115
  33. Molecular cloning of two types of GAP complementary DNA from human placenta.
    Science. 1988 Dec 23;242(4886):1697-700 PMID: 3201259
  34. C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains.
    Nature. 1992 Mar 26;356(6367):340-4 PMID: 1372395
  35. Shc products are substrates of erbB-2 kinase.
    Oncogene. 1993 Aug;8(8):2105-12 PMID: 8101647
  36. A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos.
    Cell. 1993 Apr 9;73(1):179-91 PMID: 8462098
  37. SH2 domains recognize specific phosphopeptide sequences.
    Cell. 1993 Mar 12;72(5):767-78 PMID: 7680959
  38. Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase.
    Science. 1991 Jul 26;253(5018):407-14 PMID: 1862342
  39. Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family.
    Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1746-50 PMID: 8383326
  40. SH2-containing phosphotyrosine phosphatase as a target of protein-tyrosine kinases.
    Science. 1993 Mar 12;259(5101):1607-11 PMID: 8096088
  41. Acid and base hydrolysis of phosphoproteins bound to immobilon facilitates analysis of phosphoamino acids in gel-fractionated proteins.
    Anal Biochem. 1989 Jan;176(1):22-7 PMID: 2540676
  42. Large deletions in the cytoplasmic kinase domain of the epidermal growth factor receptor do not affect its laternal mobility.
    J Cell Biol. 1986 Aug;103(2):327-31 PMID: 3015981
  43. Expression of the c-erbB-3 protein in gastrointestinal tract tumours determined by monoclonal antibody RTJ1.
    J Pathol. 1993 Jul;170(3):271-8 PMID: 8133400
  44. Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases.
    Nature. 1992 Dec 17;360(6405):689-92 PMID: 1465135
  45. Molecular cloning and expression of an additional epidermal growth factor receptor-related gene.
    Proc Natl Acad Sci U S A. 1990 Jul;87(13):4905-9 PMID: 2164210
  46. Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways.
    Cell. 1992 May 1;69(3):413-23 PMID: 1374684
  47. Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors.
    Proc Natl Acad Sci U S A. 1989 Dec;86(23):9193-7 PMID: 2687875
  48. Characterisation of human thyroid epithelial cells immortalised in vitro by simian virus 40 DNA transfection.
    Br J Cancer. 1989 Dec;60(6):897-903 PMID: 2557880
  49. Interaction of phosphatidylinositol 3-kinase-associated p85 with epidermal growth factor and platelet-derived growth factor receptors.
    Mol Cell Biol. 1992 Mar;12(3):981-90 PMID: 1372091
  50. Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells.
    Proc Natl Acad Sci U S A. 1987 Oct;84(20):7159-63 PMID: 2890160
  51. Sequence similarity of phospholipase C with the non-catalytic region of src.
    Nature. 1988 Mar 17;332(6161):269-72 PMID: 2831461
  52. cDNA cloning of a novel 85 kd protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF beta-receptor.
    Cell. 1991 Apr 5;65(1):75-82 PMID: 1849460
  53. SH2 and SH3 domains.
    Curr Biol. 1993 Jul 1;3(7):434-42 PMID: 15335710
  54. Regulation by EGF is maintained in an overexpressed chimeric EGFR/neu receptor tyrosine kinase.
    J Cell Biochem. 1990 Mar;42(3):123-33 PMID: 1969420
  55. A chimeric EGF-R-neu proto-oncogene allows EGF to regulate neu tyrosine kinase and cell transformation.
    EMBO J. 1989 Jan;8(1):159-66 PMID: 2565807
  56. Formation of phosphatidylinositol 3-phosphate by isomerization from phosphatidylinositol 4-phosphate.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9184-7 PMID: 1656463
  57. SV40-transformed simian cells support the replication of early SV40 mutants.
    Cell. 1981 Jan;23(1):175-82 PMID: 6260373
  58. An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro.
    Cell. 1993 Apr 9;73(1):169-77 PMID: 8462097
  59. A monoclonal antibody to the human epidermal growth factor receptor.
    J Cell Biochem. 1982;20(2):149-61 PMID: 6188757
  60. Expression of the c-erbB-3 protein in normal human adult and fetal tissues.
    Oncogene. 1992 Jul;7(7):1273-8 PMID: 1377811
  61. The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase.
    Science. 1990 Jan 12;247(4939):209-12 PMID: 1688471
  62. Growth factors and cancer.
    Science. 1991 Nov 22;254(5035):1146-53 PMID: 1659742
  63. Transformation by polyoma virus middle T-antigen involves the binding and tyrosine phosphorylation of Shc.
    Nature. 1994 Jan 6;367(6458):87-90 PMID: 7509037
  64. The erbB-3 gene in human pancreatic cancer.
    J Pathol. 1992 Nov;168(3):269-73 PMID: 1361525
  65. Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation.
    Nature. 1993 May 6;363(6424):45-51 PMID: 8479536
  66. A new technique for the assay of infectivity of human adenovirus 5 DNA.
    Virology. 1973 Apr;52(2):456-67 PMID: 4705382
  67. Identification of Trk binding sites for SHC and phosphatidylinositol 3'-kinase and formation of a multimeric signaling complex.
    J Biol Chem. 1993 Nov 5;268(31):22963-6 PMID: 8226808
  68. A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction.
    Cell. 1992 Jul 10;70(1):93-104 PMID: 1623525
  69. Expression of the ERBB3 gene product in breast cancer.
    Br J Cancer. 1992 Dec;66(6):1116-21 PMID: 1333787
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-06-15
Pages
2831-41
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395164
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2