Homomeric interactions between type II transforming growth factor-beta receptors.
Transforming growth factor-beta (TGF-beta) binds with high affinity to three cell-surface receptors. Both type I and II receptors are transmembrane serine/threonine kinases and thought to mediate TGF-beta responses by forming a heteromeric complex in the presence of TGF-beta. We investigated whether the type II receptors form a homomeric complex in the presence or absence of ligand. Double immunoprecipitation analyses were performed using lysates from metabolically labeled cells cotransfected with differentially epitope-tagged type II receptors. We demonstrate that the type II receptors can form a homomeric complex even in the absence of their ligand, TGF-beta. This pre-existing type II receptor complex has the ability to bind TGF-beta. Moreover, in addition to the extracellular and transmembrane domains, the cytoplasmic portions of the receptors are also able to interact with each other, indicating that multiple contact points are involved in the formation of the homomeric type II receptor complex. Our results suggest a novel mechanism of complex formation and receptor activation of the serine/threonine kinase receptor family.
Chen
R H
RH
Department of Growth and Development, University of California, San Francisco 94143-0640.
Derynck
R
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D000939:Epitopes / Q000032:analysis; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D016133:Polymerase Chain Reaction; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000302:isolation & purification / Q000378:metabolism*
D017931:DNA Primers; D000939:Epitopes; D046911:Macromolecular Substances; D009842:Oligopeptides; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta