Downloaded from http://cshperspectives.cshlp.org/ on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press Signaling Receptors for TGF-b Family Members Carl-Henrik Heldin1 and Aristidis Moustakas1,2 1Ludwig Institute for Cancer Research Ltd., Science for Life Laboratory, Uppsala University, SE-751 24 Uppsala, Sweden 2Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, SE-751 23 Uppsala, Sweden Correspondence:
[email protected] Transforming growth factor b (TGF-b) family members signal via heterotetrameric complexes of type I and type II dual specificity kinase receptors. The activation and stability of the receptors are controlled by posttranslational modifications, such as phosphorylation, ubiq- uitylation, sumoylation, and neddylation, as well as by interaction with other proteins at the cell surface and in the cytoplasm. Activation of TGF-b receptors induces signaling via formation of Smad complexes that are translocated to the nucleus where they act as tran- scription factors, as well as via non-Smad pathways, including the Erk1/2, JNK and p38 MAP kinase pathways, and the Src tyrosine kinase, phosphatidylinositol 30-kinase, and Rho GTPases. he transforming growth factor b (TGF-b) embryonic development and in the regulation Tfamily of cytokine genes has 33 human of tissue homeostasis, through their abilities to members, encoding TGF-b isoforms, bone regulate cell proliferation, migration, and differ- morphogenetic proteins (BMPs), growth and entiation. Perturbation of signaling by TGF-b differentiation factors (GDFs), activins, inhib- family members is often seen in different dis- ins, nodal, and anti-Mu¨llerian hormone (AMH) eases, including malignancies, inflammatory (Derynck and Miyazono 2008; Moustakas and conditions, and fibrotic conditions.