Identification of human activin and TGFβ type I receptors that form heteromeric kinase complexes with type II receptors

  title={Identification of human activin and TGF$\beta$ type I receptors that form heteromeric kinase complexes with type II receptors},
  author={Liliana Attisano and Juan M. Cárcamo and Francesc Ventura and F M Weis and Joan Massagu{\'e} and Jeffrey L. Wrana},

Characterization of type I receptors for transforming growth factor-beta and activin.

A systematic analysis revealed that most ALKs formed heteromeric complexes with the type II receptors for TGF-beta and activin after overexpression in COS cells; however, among the six ALK’s, only ALK-5 was a functional T GF-beta type I receptor for activation of plasminogen activator inhibitor-1, and only ALF-4 bound activin with high affinity.

Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin

It is concluded that the type I receptor subunits are primary specifiers of signals sent by TGF-beta and activin receptor complexes and do not substitute as mediators of these growth-inhibitory and extracellular matrix transcriptional responses.

Inactivation of activin-dependent transcription by kinase-deficient activin receptors.

It is indicated that kinase activities of both type II and type I receptors are required for activin signaling, and that the two types I receptors, which are expressed in a tissue-specific manner, are functionally distinct.

Formation and activation by phosphorylation of activin receptor complexes.

Analysis of the interaction between various activin receptors revealed that ActRs I and II could exist in a stable complex and that formation of that complex between transiently overexpressed molecules was not regulated by ligand, supporting a role for phosphorylation of type I ActRs in the generation of a biological signal.

Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12.

The specific interaction between the type I receptors and FKBP-12 suggests that FK BP-12 may play a role in type I receptor-mediated signaling.

Ligand-independent Activation of Transforming Growth Factor (TGF) β Signaling Pathways by Heteromeric Cytoplasmic Domains of TGF-β Receptors*

The results indicate that the cytoplasmic domains of the type I and type II TGF-β receptors physically and functionally interact with each other in the heteromeric complex.

Two distinct transmembrane serine/threonine kinases from Drosophila melanogaster form an activin receptor complex

The results indicate that the heteromeric kinase structure is a general feature of this receptor family and defines Atr-I as an activin type I receptor from D. melanogaster.

Signal transduction and TGF-beta superfamily receptors.

Although a number of transduction mechanisms may be available to TGF-beta superfamily members, evidence gathered through the use of specific kinase and G-protein inhibitors and through assays measuring activation and levels of signaling intermediates suggests that at least one signaling pathway interacts with Ras and Raf proteins via a G- protein intermediate.

Structural characterization of an activin class ternary receptor complex reveals a third paradigm for receptor specificity

The structure of GDF11/ActRIIB/Alk5 shows that, across the TGFβ family, different mechanisms regulate type I receptor binding and specificity, providing a molecular explanation for how the activin class accommodates low-affinity type I interactions without the requirement of cooperative receptor interactions.



Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor.

Combinatorial interactions and stoichiometric ratios between the type I and II receptors may determine the extent of TGF-beta binding and the resulting biological activities.

Identification of a Drosophila activin receptor.

The identification, deduced primary structure, and expression pattern of Atr-II, a receptor serine/threonine kinase found in Drosophila, is described and the possible role of an activin signaling system in Dosophila development is discussed.

A surface component on GH3 pituitary cells that recognizes transforming growth factor-beta, activin, and inhibin.

The 70-74-kDa labeled GH3 components represent a novel type of cell surface TGF-beta binding protein that is unique in its ability to recognize various other members of the T GF-beta family of bioactive polypeptides.