• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Sep 1988; 8(9): 3969–3973.
PMCID: PMC365461

Oncogenic activation of p185neu stimulates tyrosine phosphorylation in vivo.

Abstract

p185, the product of the neu/erbB2 proto-oncogene, is oncogenically activated by a point mutation that substitutes glutamic acid for valine in the transmembrane domain of the protein. We have found that the transforming form of p185 differs from its normal counterpart in inducing increased tyrosine phosphorylation of other proteins in vivo and in having a much shorter half-life. These results support the model that the transforming p185 resembles a ligand-activated receptor.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Akiyama T, Saito T, Ogawara H, Toyoshima K, Yamamoto T. Tumor promoter and epidermal growth factor stimulate phosphorylation of the c-erbB-2 gene product in MKN-7 human adenocarcinoma cells. Mol Cell Biol. 1988 Mar;8(3):1019–1026. [PMC free article] [PubMed]
  • Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science. 1986 Jun 27;232(4758):1644–1646. [PubMed]
  • Bargmann CI, Hung MC, Weinberg RA. Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185. Cell. 1986 Jun 6;45(5):649–657. [PubMed]
  • Bargmann CI, Hung MC, Weinberg RA. The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature. 1986 Jan 16;319(6050):226–230. [PubMed]
  • Bertics PJ, Gill GN. Self-phosphorylation enhances the protein-tyrosine kinase activity of the epidermal growth factor receptor. J Biol Chem. 1985 Nov 25;260(27):14642–14647. [PubMed]
  • Brown DJ, Gordon JA. The stimulation of pp60v-src kinase activity by vanadate in intact cells accompanies a new phosphorylation state of the enzyme. J Biol Chem. 1984 Aug 10;259(15):9580–9586. [PubMed]
  • Carlin CR, Knowles BB. Biosynthesis of the epidermal growth factor receptor in human epidermoid carcinoma-derived A431 cells. J Biol Chem. 1984 Jun 25;259(12):7902–7908. [PubMed]
  • Collett MS, Belzer SK, Purchio AF. Structurally and functionally modified forms of pp60v-src in Rous sarcoma virus-transformed cell lysates. Mol Cell Biol. 1984 Jul;4(7):1213–1220. [PMC free article] [PubMed]
  • Cooper JA, Sefton BM, Hunter T. Detection and quantification of phosphotyrosine in proteins. Methods Enzymol. 1983;99:387–402. [PubMed]
  • Courtneidge SA. Activation of the pp60c-src kinase by middle T antigen binding or by dephosphorylation. EMBO J. 1985 Jun;4(6):1471–1477. [PMC free article] [PubMed]
  • Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985 Dec 6;230(4730):1132–1139. [PubMed]
  • Davis RJ, Czech MP. Platelet-derived growth factor mimics phorbol diester action on epidermal growth factor receptor phosphorylation at threonine-654. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4080–4084. [PMC free article] [PubMed]
  • Decker SJ. Effects of epidermal growth factor and 12-O-tetradecanoylphorbol-13-acetate on metabolism of the epidermal growth factor receptor in normal human fibroblasts. Mol Cell Biol. 1984 Sep;4(9):1718–1724. [PMC free article] [PubMed]
  • Di Fiore PP, Pierce JH, Fleming TP, Hazan R, Ullrich A, King CR, Schlessinger J, Aaronson SA. Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells. Cell. 1987 Dec 24;51(6):1063–1070. [PubMed]
  • Di Fiore PP, Pierce JH, Kraus MH, Segatto O, King CR, Aaronson SA. erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science. 1987 Jul 10;237(4811):178–182. [PubMed]
  • Downward J, Parker P, Waterfield MD. Autophosphorylation sites on the epidermal growth factor receptor. Nature. 1984 Oct 4;311(5985):483–485. [PubMed]
  • Drebin JA, Stern DF, Link VC, Weinberg RA, Greene MI. Monoclonal antibodies identify a cell-surface antigen associated with an activated cellular oncogene. Nature. 1984 Dec 6;312(5994):545–548. [PubMed]
  • Gilmore T, DeClue JE, Martin GS. Protein phosphorylation at tyrosine is induced by the v-erbB gene product in vivo and in vitro. Cell. 1985 Mar;40(3):609–618. [PubMed]
  • Glenney JR, Jr, Chen WS, Lazar CS, Walton GM, Zokas LM, Rosenfeld MG, Gill GN. Ligand-induced endocytosis of the EGF receptor is blocked by mutational inactivation and by microinjection of anti-phosphotyrosine antibodies. Cell. 1988 Mar 11;52(5):675–684. [PubMed]
  • Honegger AM, Dull TJ, Felder S, Van Obberghen E, Bellot F, Szapary D, Schmidt A, Ullrich A, Schlessinger J. Point mutation at the ATP binding site of EGF receptor abolishes protein-tyrosine kinase activity and alters cellular routing. Cell. 1987 Oct 23;51(2):199–209. [PubMed]
  • Hung MC, Schechter AL, Chevray PY, Stern DF, Weinberg RA. Molecular cloning of the neu gene: absence of gross structural alteration in oncogenic alleles. Proc Natl Acad Sci U S A. 1986 Jan;83(2):261–264. [PMC free article] [PubMed]
  • Hunter T, Cooper JA. Epidermal growth factor induces rapid tyrosine phosphorylation of proteins in A431 human tumor cells. Cell. 1981 Jun;24(3):741–752. [PubMed]
  • Kamps MP, Sefton BM. Identification of multiple novel polypeptide substrates of the v-src, v-yes, v-fps, v-ros, and v-erb-B oncogenic tyrosine protein kinases utilizing antisera against phosphotyrosine. Oncogene. 1988 Apr;2(4):305–315. [PubMed]
  • King CR, Kraus MH, Aaronson SA. Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science. 1985 Sep 6;229(4717):974–976. [PubMed]
  • Kmiecik TE, Shalloway D. Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation. Cell. 1987 Apr 10;49(1):65–73. [PubMed]
  • Kraus MH, Popescu NC, Amsbaugh SC, King CR. Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. EMBO J. 1987 Mar;6(3):605–610. [PMC free article] [PubMed]
  • Padhy LC, Shih C, Cowing D, Finkelstein R, Weinberg RA. Identification of a phosphoprotein specifically induced by the transforming DNA of rat neuroblastomas. Cell. 1982 Apr;28(4):865–871. [PubMed]
  • Parker RC, Varmus HE, Bishop JM. Expression of v-src and chicken c-src in rat cells demonstrates qualitative differences between pp60v-src and pp60c-src. Cell. 1984 May;37(1):131–139. [PubMed]
  • Piwnica-Worms H, Saunders KB, Roberts TM, Smith AE, Cheng SH. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell. 1987 Apr 10;49(1):75–82. [PubMed]
  • Rosen OM, Herrera R, Olowe Y, Petruzzelli LM, Cobb MH. Phosphorylation activates the insulin receptor tyrosine protein kinase. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3237–3240. [PMC free article] [PubMed]
  • Roussel MF, Dull TJ, Rettenmier CW, Ralph P, Ullrich A, Sherr CJ. Transforming potential of the c-fms proto-oncogene (CSF-1 receptor). Nature. 1987 Feb 5;325(6104):549–552. [PubMed]
  • Schechter AL, Hung MC, Vaidyanathan L, Weinberg RA, Yang-Feng TL, Francke U, Ullrich A, Coussens L. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science. 1985 Sep 6;229(4717):976–978. [PubMed]
  • Schechter AL, Stern DF, Vaidyanathan L, Decker SJ, Drebin JA, Greene MI, Weinberg RA. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 1984 Dec 6;312(5994):513–516. [PubMed]
  • Schubert D, Heinemann S, Carlisle W, Tarikas H, Kimes B, Patrick J, Steinbach JH, Culp W, Brandt BL. Clonal cell lines from the rat central nervous system. Nature. 1974 May 17;249(454):224–227. [PubMed]
  • Sefton BM, Beemon K, Hunter T. Comparison of the expression of the src gene of Rous sarcoma virus in vitro and in vivo. J Virol. 1978 Dec;28(3):957–971. [PMC free article] [PubMed]
  • Sefton BM, Hunter T, Beemon K, Eckhart W. Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus. Cell. 1980 Jul;20(3):807–816. [PubMed]
  • Semba K, Kamata N, Toyoshima K, Yamamoto T. A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6497–6501. [PMC free article] [PubMed]
  • Shalloway D, Coussens PM, Yaciuk P. Overexpression of the c-src protein does not induce transformation of NIH 3T3 cells. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7071–7075. [PMC free article] [PubMed]
  • Shih C, Padhy LC, Murray M, Weinberg RA. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature. 1981 Mar 19;290(5803):261–264. [PubMed]
  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. [PubMed]
  • Stern DF, Heffernan PA, Weinberg RA. p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity. Mol Cell Biol. 1986 May;6(5):1729–1740. [PMC free article] [PubMed]
  • Stern DF, Kamps MP. EGF-stimulated tyrosine phosphorylation of p185neu: a potential model for receptor interactions. EMBO J. 1988 Apr;7(4):995–1001. [PMC free article] [PubMed]
  • Stern DF, Roberts AB, Roche NS, Sporn MB, Weinberg RA. Differential responsiveness of myc- and ras-transfected cells to growth factors: selective stimulation of myc-transfected cells by epidermal growth factor. Mol Cell Biol. 1986 Mar;6(3):870–877. [PMC free article] [PubMed]
  • Sturani E, Zippel R, Toschi L, Morello L, Comoglio PM, Alberghina L. Kinetics and regulation of the tyrosine phosphorylation of epidermal growth factor receptor in intact A431 cells. Mol Cell Biol. 1988 Mar;8(3):1345–1351. [PMC free article] [PubMed]
  • Velu TJ, Beguinot L, Vass WC, Willingham MC, Merlino GT, Pastan I, Lowy DR. Epidermal-growth-factor-dependent transformation by a human EGF receptor proto-oncogene. Science. 1987 Dec 4;238(4832):1408–1410. [PubMed]
  • Venter DJ, Tuzi NL, Kumar S, Gullick WJ. Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: immunohistological assessment correlates with gene amplification. Lancet. 1987 Jul 11;2(8550):69–72. [PubMed]
  • Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T, Toyoshima K. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986 Jan 16;319(6050):230–234. [PubMed]
  • Yokota J, Yamamoto T, Toyoshima K, Terada M, Sugimura T, Battifora H, Cline MJ. Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo. Lancet. 1986 Apr 5;1(8484):765–767. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...