Cell
Volume 71, Issue 6, 11 December 1992, Pages 1003-1014
Journal home page for Cell

Article
TGFβ signals through a heteromeric protein kinase receptor complex

https://doi.org/10.1016/0092-8674(92)90395-SGet rights and content

Abstract

Transforming growth factor β (TGFβ) binds with high affinity to the type II receptor, a transmembrane protein with a cytoplasmic serine/threonine kinase domain. We show that the type II receptor requires both its kinase activity and association with another TGFβ-binding protein, the type I receptor, to signal growth inhibition and early gene responses. Receptors I and II associate as interdependent components of a heteromeric complex: receptor I requires receptor II to bind TGFβ, and receptor II requires receptor I to signal. This mode of operation points to fundamental differences between this receptor and the protein-tyrosine kinase cytokine receptors.

References (51)

  • L.L. Georgi et al.

    daf-1, a C. elegans gene controlling dauer larva development, encodes a novel receptor protein kinase

    Cell

    (1990)
  • A. Gougos et al.

    Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells

    J. Biol. Chem.

    (1990)
  • M.R. Keeton et al.

    Identification of regulatory sequences in the type 1 plasminogen activator inhibitor gene responsive to transforming growth factor β

    J. Biol. Chem.

    (1991)
  • M. Kondo et al.

    Activin receptor mRNA is expressed early in Xenopus embryogenesis and the level of the expression affects the body axis formation

    Biochem. Biophys. Res. Commun.

    (1991)
  • M. Laiho et al.

    Concomitant loss of transforming growth factor-β receptor types I and II in cell mutants resistant to TGF-β

    J. Biol. Chem.

    (1990)
  • M. Laiho et al.

    Responsiveness to transforming growth factor-β restored by complementation between cells defective in TGF-β receptors I and II

    J. Biol. Chem.

    (1991)
  • H.Y. Lin et al.

    Expression cloning of the TGF-β type II receptor, a functional transmembrane serine/threonine kinase

    Cell

    (1992)
  • Y.-S. Lin et al.

    GAL4 derivatives function alone and synergistically with mammalian activators in vitro

    Cell

    (1988)
  • F. López-Casillas et al.

    Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-β receptor system

    Cell

    (1991)
  • K. MacKay et al.

    Novel 150- and 170-kDa glycoproteins that bind transforming growth factor (TGF)-β1 but not TGF-β2 are present in several cell lines

    J. Biol. Chem.

    (1991)
  • J. Massagué

    Identification of receptors of type β transforming growth factor

    Meth. Enzymol.

    (1987)
  • J. Massagué

    Receptors for the TGF-β family

    Cell

    (1992)
  • L.S. Mathews et al.

    Expression cloning of an activin receptor, a predicted transmembrane serine kinase

    Cell

    (1991)
  • T. Nakamura et al.

    Isolation and characterization of activin receptor from mouse embryonal carcinoma cells

    J. Biol. Chem.

    (1992)
  • P. O'Grady et al.

    Purification of a new type high molecular weight receptor (type V receptor) of transforming growth factor β from bovine liver

    J. Biol. Chem.

    (1991)
  • Cited by (1447)

    View all citing articles on Scopus

    Present address: Department of Virology, University of Helsinki, 00290 Helsinki, Finland.

    View full text