Product Information

Transforming Growth Factor β Receptor (TGFBR) Family

The transforming growth factor β (TGFβ) superfamily of ligands are pleiotropic cytokines that regulate a diverse range of cellular processes, including cell proliferation, differentiation, migration, adhesion and death. The superfamily of ligands include: Activin, Nodal, TGFβ, BMP (bone morphogenetic protein), GDF (growth and differentiation factor), and AMH (anti-müllerian hormone). They elicit signaling pathways that are evolutionarily conserved and involved in the cellular processes in both adult organisms and developing embryos. The signaling begins with the engagement of a ligand with a type II TGFβ receptor (TGFBR), which in turn recruits and activates a type I receptor. Both type receptors contain a cysteine-rich extracellular domain (ECD), a transmembrane (TM) domain and a cytoplasmic serine/threonine kinase (STK) domain. The TGFBR family is the only receptor family with such a STK activity. The type I receptors differ from the type II receptors by the presence of a conserved 30-amino acid stretch of glycine-serine (GS) repeats before the kinase domain (see the schematic diagram below).  The binding of a ligand causes the conformational change in a type II receptor so that its cytoplasmic kinase domain is in a catalytically favorable orientation. The type II receptor then phosphorylates and activates a type I receptor, which eventually phosphorylates the downstream SMAD family transcription factors for the regulation of target gene expression. 

In mammals there are 5 type II receptors and 7 known type I receptors (see the diagram above). Each class of TGFβ ligands appears to bind to a specific type II receptor (see the summary table below). For example, the TGFβ family ligands, including TGFβ1, TGFβ2, and TGFβ3, bind TGFBR2 and are involved in embryogenesis, cell differentiation, apoptosis and many other functions. The Activin family ligands, including Activin A, Activin B and Activin AB, bind ACVR2A (activin A receptor type IIA) and are involved in embryogenesis and osteogenesis.  Activins also regulate many hormones including pituitary, gonadal and hypothalamic hormones as well as insulin. In addition they may serve as nerve cell survival factors.  Nodal binds to ACVR2B and can then either form a receptor complex with ACVR1B or ACVR1C.  Nodal is involved in left and right axis specification, as well as mesoderm and endoderm induction.  AMH binds AMHR2 and inhibits the development of the Müllerian ducts (paramesonephric ducts) in the male embryo.  Unlike other ligands, the BMP family ligands recognize both type I and type II receptors with high affinity only when both type receptors are present. They are involved in osteogenesis, cell growth & differentiation, anterior-posterior axis specification, and homeostasis.  

A unique feature of TGFBR signaling is the existence of diverse binding proteins that are not related by sequence but can act as functional antagonists or agonists. There are several classes of binding proteins, including Follistatin, Chordin, Noggin, and DAN. They differ in their ligand affinity as well as their mode of regulation. For example, Follistatin acts as a binding protein to BMP4 without competing with type I receptor binding whereas Noggin and Chordin directly compete for receptor binding. Follistatin also binds and inhibits Activin. Members of the DAN family, Cerberus, DAN, and Gremlin, also antagonize TGFβ family ligands. They contain 9 conserved cysteines, which can form disulfide bridges.  DAN also antagonizes GDF family members, such as GDF5, GDF6 and GDF7.  Lefty is a regulator of TGFβ ligands and is involved in the axis patterning during embryogenesis. BMP and Activin membrane bound inhibitor (BAMBI), has a similar extracellular domain as a type I receptor but lacks a serine/threonine protein kinase domain. It binds to the type I receptor preventing it from being activated, therefore serving as a negative regulator for the signaling.  An additional TGFβ receptor type III (TGFBR3) that lacks catalytic activity or signaling domain can form a complex with TGFBR1 and TGFBR2 to enhance their binding to TGFβ ligands.  

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TGFBR Family Related Genes, Proteins and Antibodies

G&P Biosciences provide a comprehensive list of products and services for TGFβ family ligands and receptors R&D.  We offer 100% sequence verified full-length cDNA clones for all known TGFBR related genes as well as pre-packaged high-titer lentiviral particles.  The pre-packaged lentiviral particles are ready to transduce any mammalian cell types to generate stable expressing cell lines with the choice of multiple antibiotics selection markers available. We also offer highly purified recombinant proteins (either as a Fc-fusion or with a His-tag) for all TGFBR family members.  Additionally we offer recombinant monoclonal antibodies that target TGFBRs with high affinity and specificity.  Many of these antibodies efficiently block or activate TGFBR-mediated signaling pathways.      

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