Cell
Volume 48, Issue 3, 13 February 1987, Pages 429-440
Journal home page for Cell

Article
Different transforming growth factor-α species are derived from a glycosylated and palmitoylated transmembrane precursor

https://doi.org/10.1016/0092-8674(87)90194-2Get rights and content

Abstract

cDNA analysis has revealed that the 50 amino acid transforming growth factor-α (TGF-α) is derived from a 160 amino acid precursor. Antibodies to TGF-α and to a C-terminal portion of the precursor were used to study the biosynthesis and processing of the precursor. CHO cells transfected with a TGF-α expression vector secrete high levels of TGF-α; a mixture of species of about 18 kd is secreted in addition to the 50 amino acid form. These larger species are N-glycosylated and are derived from the same precursor as the smaller form. The C-terminal segment of the precursor remains anchored in the membrane and has covalently attached palmitate. The newly synthesized TGF-α precursor is thus a transmembrane protein that subsequently undergoes external proteolytic cleavages, releasing several TGF-α species.

References (62)

  • H. Marquardt et al.

    Human transforming growth factor

    Production by a melanoma cell line, purification and initial characterization

    J. Biol. Chem.

    (1982)
  • J. Massagué

    Epidermal growth factor-like transforming growth factor. I. Isolation, chemical characterization and potentiation by other transforming growth factors from feline sarcoma virus-transformed rat cells

    J. Biol. Chem.

    (1983)
  • J. Massagué

    Epidermal growth factor-like transforming growth factor receptors in human plasma membranes on A431 cells

    J. Biol. Chem.

    (1983)
  • R. Muller

    Calculation of average antibody affinity in anti-hapten sera from data obtained by competitive radioimmunoassay

    J. Immunol. Methods

    (1980)
  • J.J. Nestor et al.

    A synthetic fragment of rat transforming growth factor α with receptor binding and antigenic properties

    Biochim. Biophys. Res. Commun.

    (1985)
  • H. Oppermann et al.

    The structure and protein kinase activity of proteins encoded by nonconditional mutants and back mutants in the src gene of avian sarcoma virus

    Virology

    (1981)
  • D. Perlman et al.

    A putative signal peptidase recognition site and sequence in eukaryotic and prokaryotic signal peptides

    J. Mol. Biol.

    (1983)
  • A. Rosenthal et al.

    Expression in rat fibroblasts of a human transforming growth factor-α cDNA results in transformation

    Cell

    (1986)
  • M.J. Schlesinger et al.

    Fatty acid acylation of proteins in cultured cells

    J. Biol. Chem.

    (1980)
  • M.F.G. Schmidt et al.

    Fatty acid binding to vesicular stomatitis virus glycoprotein: a new type of post-translational modification of the viral glycoprotein

    Cell

    (1979)
  • B.M. Sefton et al.

    The transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus contain tightly bound lipid

    Cell

    (1982)
  • P. Stroobant et al.

    Purification and characterization of vaccinia virus growth factor

    Cell

    (1985)
  • R.L. Vandlen et al.

    Purification and characterization of plasma membrane fractions from cultured pituitary cells

    Biochim. Biophys. Acta.

    (1981)
  • M.E. Winkler et al.

    The purification of fully active recombinant transforming growth factor α produced in Escherichia coli

    J. Biol. Chem.

    (1986)
  • F. Wold

    Fatty acylation of proteins (keep fit with fat?)

    Trends Biochem. Sci.

    (1986)
  • G. Barany et al.

    Solid phase peptide synthesis

  • L.L. Dart et al.

    Transforming growth factors from a human tumor cell: characterization of transforming growth factor-β and identification of high molecular weight transforming growth factor-α

    Biochemistry

    (1985)
  • J.E. De Larco et al.

    Growth factors from murine sarcoma virus-transformed cells

  • J. De Larco et al.

    Ectopic peptides released by a human melanoma cell line that modulate the transformed phenotype

  • R. Derynck et al.

    Synthesis of mRNAs for transforming growth factors α and β and the epidermal growth factor receptor by human tumor cells

    Cancer Res.

    (1987)
  • D.A. Eppstein et al.

    Epidermal growth factor receptor occupancy inhibits vaccinia virus infection

    Nature

    (1985)
  • Cited by (203)

    • ADAM17 orchestrates Interleukin-6, TNFα and EGF-R signaling in inflammation and cancer

      2022, Biochimica et Biophysica Acta - Molecular Cell Research
      Citation Excerpt :

      Only several years later it was realized that TNFα was a type II membrane protein, which was processed by an unknown protease to release the mature, soluble TNFα protein [2,3]. By that time it was already known that growth factors such as epidermal growth factor (EGF) [4] or tumor growth factor alpha (TGFα) [5] are synthesized as transmembrane precursors and it was speculated that these proteins were cleaved by an unknown protease to release the active, soluble growth factor [4,5]. Interestingly, around the same time, it was also found that the two types of TNF receptors (TNF-RI and TNF-RII) occurred as truncated, soluble proteins in the supernatant of cells and in some body fluids [6].

    • Discovery of novel inhibitors of a disintegrin and metalloprotease 17 (ADAM17) using glycosylated and non-glycosylated substrates

      2012, Journal of Biological Chemistry
      Citation Excerpt :

      ADAM substrates exhibit various degrees of glycosylation, whereas distances of glycosylation sites from respective scissile bonds also vary significantly. For example, the cleavage site of TNFα by ADAM17 is only four residues away from a glycosylated residue (46), whereas glycosylation occurs 14 residues away from the TGFα cleavage site (47) and more than 200 residues away from the L-selectin cleavage site (48). In this work, we have investigated the role of glycosylation in the specificity of ADAM-catalyzed reactions using TNFα as a model substrate.

    • Growth Factors in the Gastrointestinal Tract

      2012, Physiology of the Gastrointestinal Tract, Two Volume Set
    • Growth Factors in the Gastrointestinal Tract

      2012, Physiology of the Gastrointestinal Tract
    View all citing articles on Scopus

    Present address: Center for Thrombosis and Vascular Research, University of Leuven, Campus Gasthuisberg, B-3000 Leuven, Belgium.

    View full text