TGFB type II-type III receptor fusions
Certain embodiments are directed to novel heterotrimeric fusions in which the ectodomain of the TGF-β type II receptor (TβP?II) is coupled to the N- and C-terminal ends of the endoglin-domain of the TGF-β type III receptor (TpRIIIE). Certain embodiments are directed to novel heterotrimeric polypeptides in which the ectodomain of the TGF-β type II receptor (TI3RII) is coupled to the N- and C-terminal ends of the endoglin-domain (E domain) of the TGF-β type III receptor (TI3RIII). This trimeric receptor, known as RER, can bind all three TGF-β isoforms with sub-nanomolar affinity and is effective at neutralizing signaling induced by all three TGF-β isoforms, but not other ligands of the TGF-β superfamily, such as activins, growth and differentiation factors (GDFs), and bone morphonogenetic proteins (BMPs).
1. A TGFβ-binding heterotrimeric fusion protein wherein the fusion protein has an amino acid sequence that is 90% identical to SEQ ID NO: 2.
2. The fusion protein of claim 1 , further comprising an amino terminal signal sequence.
3. The fusion protein of claim 1 , further comprising an amino terminal or carboxy terminal tag.
4. The fusion protein of claim 3 , wherein the tag is a carboxy terminal hexa-histidine.
5. A method of treating a condition related to increased expression TGFβ comprising administering an effective amount of the fusion protein of claim 1 to subject in thereof.
6. The method of claim 5 , wherein the condition is a hyperproliferative disorder.
7. The method of claim 6 , wherein the hyperproliferative disorder is cancer.
8. The method of claim 5 , wherein the condition is fibrosis.
9. A heterotrimeric fusion protein wherein the fusion protein has the amino acid sequence of SEQ ID NO:2.
10. The fusion protein of claim 9 , further comprising an amino terminal signal sequence.
11. The fusion protein of claim 9 , further comprising an amino terminal or carboxy terminal tag.
12. The fusion protein of claim 11 , wherein the tag is a carboxy terminal hexa-Histidine.