A chimeric serine/threonine kinase receptor system reveals the potential of multiple type II receptors to cooperate with transforming growth factor-beta type I receptor.
Receptor-type serine/threonine kinases (RSKs) have been organized into two distinct classes known as types I and II on the basis of sequence similarity. However, experiments have shown ligand specificities in the two classes and as a result type I and type II receptors can often bind to a common ligand. The transforming growth factor-beta- (TGF-beta) specific receptors represent such a case, where both type I and II receptors (T beta RI and T beta RII) are observed. Of additional interest is the observation that heteromeric associations of type I and II receptors can also enable signaling. To further elucidate the function of various RSKs, the extracellular domains of both alpha and beta chains from human granulocyte-macrophage colony-stimulating factor receptors were linked to transmembrane cytoplasmic domains of RSKs. Chimeric receptors of human granulocyte-macrophage receptor (hGMR) alpha with T beta RI and hGMR beta with T beta RII were expressed in murine pre-B cell-derived Ba/F3 cells. These chimeras formed heteromeric complexes, transmitted TGF-beta signals, and were down-modulated in response to human granulocyte-macrophage colony-stimulating factor. However, experiments utilizing these chimeric receptors in different combinations revealed that only heteromeric associations of transmembrane cytoplasmic domains mediated signaling and down-modulation. Chimeric receptors with transmembrane cytoplasmic domains of activin receptor type II and bone morphogenetic protein receptor type II also provided signals in conjunction with chimeric T beta RI. As a result, these type II receptors may share a common potential to signal via T beta RI. hGMR-RSK chimeric receptors may be useful tools for the identification and characterization of the divergent signals mediated by individual RSKs.
Muramatsu
M
M
Department of Molecular and Developmental Biology, University of Tokyo, Japan.
Yan
J
J
Eto
K
K
Tomoda
T
T
Yamada
R
R
Arai
K
K
D030201:Activin Receptors, Type I; D000818:Animals; D012831:Bombyx; D019556:COS Cells; D002460:Cell Line; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000187:drug effects; D017978:Receptors, Growth Factor / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects
D006131:Growth Inhibitors; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I