Home LiteratureArticle Details
PMID: 2927393 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Molecular and biochemical characterization of the human trk proto-oncogene.

Molecular and cellular biology ·Vol. 9 ·No. 1 ·1989-01-00 ·Pages 24-33

Martin-Zanca D, Oskam R, Mitra G, Copeland T, Barbacid M

Abstract

Molecular analysis of the human trk oncogene, a transforming gene isolated from a colon carcinoma biopsy, revealed the existence of a novel member of the tyrosine kinase gene family. This locus, which we now designate the trk proto-oncogene, codes for a protein of 790 amino acid residues that has several features characteristic of cell surface receptors. They include (i) a 32-amino-acid-long putative signal peptide, (ii) an amino-terminal moiety (residues 33 to 407) rich in consensus sites for N-glycosylation, (iii) a transmembrane domain, (iv) a kinase catalytic region highly related to that of other tyrosine kinases, and (v) a very short (15 residue) carboxy-terminal tail. Residues 1 to 392 were absent in the trk oncogene, as they were replaced by tropomyosin sequences. However, no other differences were found between the transforming and nontransforming trk alleles (residues 392 to 790), suggesting that no additional mutations are required to activate the transforming potential of this gene. The human trk proto-oncogene codes for a 140,000-dalton glycoprotein, designated gp140proto-trk. However, its primary translational product is a 110,000-dalton glycoprotein which becomes immediately glycosylated, presumably during its translocation into the endoplasmic reticulum. This molecule, designated gp110proto-trk, is further glycosylated to yield the mature form, gp140proto-trk. Both gp110proto-trk and gp140proto-trk proteins possess in vitro kinase activity specific for tyrosine residues. Finally, iodination of intact NIH 3T3 cells expressing trk proto-oncogene products indicated that only the mature form, gp140proto-trk, cross the plasma membrane, becoming exposed to the outside of the cell. These results indicate that the product of the human trk locus is a novel tyrosine kinase cell surface receptor for an as yet unknown ligand.

MeSH Terms
Amino Acid Sequence Base Sequence DNA/isolation & purification DNA, Recombinant/analysis Gene Expression Regulation Genetic Vectors Humans Molecular Sequence Data Plasmids Precipitin Tests Protein-Tyrosine Kinases/genetics Proto-Oncogene Mas Proto-Oncogenes
Chemicals
DNA, Recombinant MAS1 protein, human Proto-Oncogene Mas DNA Protein-Tyrosine Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Martin-Zanca D
Section of Developmental Oncology, National Cancer Institute Frederick Cancer Research Facility, Maryland 21701.
Oskam R
Mitra G
Copeland T
Barbacid M
References (51)
51 references, click to expand
  1. Transfer of proteins across membranes.
    Annu Rev Biochem. 1981;50:317-48 PMID: 7023361
  2. Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus.
    Cell. 1980 Jul;20(3):807-16 PMID: 6251974
  3. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter.
    J Mol Appl Genet. 1982;1(4):327-41 PMID: 6286831
  4. Oncogenes in solid human tumours.
    Nature. 1982 Dec 9;300(5892):539-42 PMID: 7144906
  5. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences.
    Nature. 1984 Feb 9-15;307(5951):521-7 PMID: 6320011
  6. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  7. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells.
    Nature. 1984 May 31-Jun 6;309(5967):418-25 PMID: 6328312
  8. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing.
    Gene. 1984 Jun;28(3):351-9 PMID: 6235151
  9. Molecular cloning of a new transforming gene from a chemically transformed human cell line.
    Nature. 1984 Sep 6-11;311(5981):29-33 PMID: 6590967
  10. Protein kinase C phosphorylation of the EGF receptor at a threonine residue close to the cytoplasmic face of the plasma membrane.
    Nature. 1984 Oct 4-10;311(5985):480-3 PMID: 6090944
  11. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen.
    Nature. 1984 Dec 6-12;312(5994):513-6 PMID: 6095109
  12. Rapid and efficient site-specific mutagenesis without phenotypic selection.
    Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 PMID: 3881765
  13. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes.
    Nature. 1985 Feb 28-Mar 6;313(6005):756-61 PMID: 2983222
  14. Tumor-promoting phorbol diesters cause the phosphorylation of epidermal growth factor receptors in normal human fibroblasts at threonine-654.
    Proc Natl Acad Sci U S A. 1985 Apr;82(7):1974-8 PMID: 2984676
  15. The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling.
    Cell. 1985 Apr;40(4):747-58 PMID: 2859121
  16. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1.
    Cell. 1985 Jul;41(3):665-76 PMID: 2408759
  17. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia.
    Nature. 1985 Jun 13-19;315(6020):550-4 PMID: 2989692
  18. Structure and expression of the human haptoglobin locus.
    EMBO J. 1985 Jan;4(1):119-26 PMID: 4018023
  19. Protein-tyrosine kinases.
    Annu Rev Biochem. 1985;54:897-930 PMID: 2992362
  20. Activation of a novel human transforming gene, ret, by DNA rearrangement.
    Cell. 1985 Sep;42(2):581-8 PMID: 2992805
  21. The human met oncogene is related to the tyrosine kinase oncogenes.
    Nature. 1985 Nov 28-Dec 4;318(6044):385-8 PMID: 4069211
  22. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene.
    Science. 1985 Dec 6;230(4730):1132-9 PMID: 2999974
  23. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor.
    Nature. 1986 Jan 16-22;319(6050):230-4 PMID: 3003577
  24. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences.
    Nature. 1986 Feb 27-Mar 5;319(6056):743-8 PMID: 2869410
  25. Tyr527 is phosphorylated in pp60c-src: implications for regulation.
    Science. 1986 Mar 21;231(4744):1431-4 PMID: 2420005
  26. Protein kinase C phosphorylation at Thr 654 of the unoccupied EGF receptor and EGF binding regulate functional receptor loss by independent mechanisms.
    Cell. 1986 Mar 28;44(6):839-48 PMID: 3006920
  27. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus.
    Nature. 1986 Mar 20-26;320(6059):277-80 PMID: 2421165
  28. A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family.
    Nature. 1986 Apr 3-9;320(6061):415-21 PMID: 3007997
  29. Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors.
    Nature. 1986 Sep 18-24;323(6085):226-32 PMID: 3020426
  30. Bifunctional messenger RNAs in eukaryotes.
    Cell. 1986 Nov 21;47(4):481-3 PMID: 3779834
  31. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity.
    EMBO J. 1986 Oct;5(10):2503-12 PMID: 2877871
  32. Human c-ros-1 gene homologous to the v-ros sequence of UR2 sarcoma virus encodes for a transmembrane receptorlike molecule.
    Mol Cell Biol. 1986 Aug;6(8):3000-4 PMID: 3023956
  33. Transforming potential of the c-fms proto-oncogene (CSF-1 receptor).
    Nature. 1987 Feb 5-11;325(6104):549-52 PMID: 3027579
  34. Sevenless, a cell-specific homeotic gene of Drosophila, encodes a putative transmembrane receptor with a tyrosine kinase domain.
    Science. 1987 Apr 3;236(4797):55-63 PMID: 2882603
  35. Molecular characterization of the human trk oncogene.
    Cold Spring Harb Symp Quant Biol. 1986;51 Pt 2:983-92 PMID: 3472772
  36. ret transforming gene encodes a fusion protein homologous to tyrosine kinases.
    Mol Cell Biol. 1987 Apr;7(4):1378-85 PMID: 3037315
  37. Biosynthetic protein transport and sorting by the endoplasmic reticulum and Golgi.
    Annu Rev Biochem. 1987;56:829-52 PMID: 3304148
  38. Receptors for epidermal growth factor and other polypeptide mitogens.
    Annu Rev Biochem. 1987;56:881-914 PMID: 3039909
  39. A thousand and one protein kinases.
    Cell. 1987 Sep 11;50(6):823-9 PMID: 3113737
  40. Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors.
    Proc Natl Acad Sci U S A. 1987 Sep;84(18):6379-83 PMID: 2819873
  41. Identification and biochemical characterization of p70TRK, product of the human TRK oncogene.
    Proc Natl Acad Sci U S A. 1987 Oct;84(19):6707-11 PMID: 3477801
  42. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.
    Nucleic Acids Res. 1987 Oct 26;15(20):8125-48 PMID: 3313277
  43. A novel putative tyrosine kinase receptor encoded by the eph gene.
    Science. 1987 Dec 18;238(4834):1717-20 PMID: 2825356
  44. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand.
    EMBO J. 1987 Nov;6(11):3341-51 PMID: 2448137
  45. Rapid and efficient site-specific mutagenesis without phenotypic selection.
    Methods Enzymol. 1987;154:367-82 PMID: 3323813
  46. A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas.
    Cell. 1988 Jan 29;52(2):185-95 PMID: 3277717
  47. Activation of the receptor kinase domain of the trk oncogene by recombination with two different cellular sequences.
    EMBO J. 1988 Jan;7(1):147-54 PMID: 2966065
  48. A new technique for the assay of infectivity of human adenovirus 5 DNA.
    Virology. 1973 Apr;52(2):456-67 PMID: 4705382
  49. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  50. Surface-specific iodination of membrane proteins of viruses and eucaryotic cells using 1,3,4,6-tetrachloro-3alpha,6alpha-diphenylglycoluril.
    Biochemistry. 1978 Oct 31;17(22):4807-17 PMID: 215191
  51. Genetic structure and transforming sequence of avian sarcoma virus UR2.
    J Virol. 1982 Mar;41(3):833-41 PMID: 6284974
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.9.1.24-33.1989
Published
1989-01-00
Pages
24-33
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC362141
Subset
IM
Grants
NCI NIH HHS · N01-CO-74101 · United States
Databases
GENBANK
M23102
External Links
PubMed source DOI: 10.1128/mcb.9.1.24-33.1989 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