Isolated nucleic acid molecule comprising the amino acid sequence of SEQ ID NO:1
The present invention provides novel activin IIB5 receptor polypeptides capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the receptor polypeptides. Compositions and methods for treating muscle-wasting, metabolic and other disorders are also provided.
1. An isolated nucleic acid molecule comprising a polynucleotide selected from the group consisting of:
(a) a polynucleotide consisting of the sequence set forth in SEQ ID NO: 1;
(b) a polynucleotide encoding a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 2; and
(c) a polynucleotide encoding a polypeptide consisting of an amino acid sequence at least 95% identical to SEQ ID NO: 2, wherein the polypeptide is capable of binding myostatin, activin A or GDF-11.
2. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule further comprises polynucleotides encoding at least one heterologous protein in frame with the polynucleotides set forth in claim 1 .
3. The isolated nucleic acid molecule of claim 2 , wherein heterologous protein is an Fc polypeptide.
4. The isolated nucleic acid molecule of claim 3 , wherein the Fc polypeptide is attached by a linker peptide.
5. A recombinant vector that directs the expression of the nucleic acid molecule of claim 1 .
6. An isolated host cell comprising the recombinant vector of claim 5 .
7. The host cell of claim 6 wherein the host cell is a mammalian cell.
8. A method of producing an activin IIB5 receptor polypeptide comprising culturing the host cell of claim 6 under conditions promoting expression of the polypeptide, and recovering the polypeptide.
9. An isolated nucleic acid molecule comprising a polynucleotide consisting of the sequence set forth in SEQ ID NO: 1.
10. The nucleic acid molecule of any one of claims 1 and 2 through 9 , wherein the polynucleotide is operably linked to a transcriptional or translational regulatory sequence.
11. The nucleic acid molecule of claim 10 wherein the transcriptional or translational sequence comprises a transcriptional promoter or enhancer.