title: Constitutive homo- and hetero-oligomerization of TbetaRII-B, an alternatively spliced variant of the mouse TGF-beta type II receptor.
abstract: Transforming growth factor (TGF)-beta ligands signal through transmembrane type I and type II serine/threonine kinase receptors, which form heteromeric signalling complexes upon ligand binding. Type II TGF-beta receptors (TbetaRII) are reported to exist as homodimers at the cell surface, but the oligomerization pattern and dynamics of TbetaRII splice variants in live cells has not been demonstrated thus far. Using co-immunoprecipitation and bioluminescence resonance energy transfer (BRET), we demonstrate that the mouse TbetaRII receptor splice variant TbetaRII-B is capable of forming ligand-independent homodimers and heterodimers with TbetaRII. The homomeric interaction of mouse (m)TbetaRII-B isoforms, however, is less robust than the heteromeric interactions of mTbetaRII-B with wild-type TbetaRII, which indicates that these receptors may be more likely to heterodimerize when both receptors are expressed. Moreover, we demonstrate that mTbetaRII-B is a signalling receptor with ubiquitous tissue expression. Our study thus demonstrates previously unappreciated complex formation of TGF-beta type II receptors, and suggests that mTbetaRII-B can direct TGF-beta-induced signalling in vitro and in vivo.
authors.affiliation: Department of Medicine II, University of Giessen Lung Center, Justus-Liebig University, Giessen, Germany.
authors.forename: Manda S
authors.initials: MS
authors.lastname: Krishnaveni
authors.forename: Jakob Lerche
authors.initials: JL
authors.lastname: Hansen
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Rory E
authors.initials: RE
authors.lastname: Morty
authors.forename: Søren P
authors.initials: SP
authors.lastname: Sheikh
authors.forename: Oliver
authors.initials: O
authors.lastname: Eickelberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D019281:Dimerization; D014644:Genetic Variation / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009928:Organ Specificity; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D022821:RNA Splice Sites / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry* / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: D020033:Protein Isoforms; D022821:RNA Splice Sites; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II