Variants derived from ActRIIB and uses therefor
In certain aspects, the present invention provides compositions and methods for modulating (promoting or inhibiting) growth of a tissue, such as bone, cartilage, muscle, fat, and/or neuronal tissue. The present invention also provides methods of screening compounds that modulate activity of an ActRIIB protein and/or an ActRIIB ligand. The compositions and methods provided herein are useful in treating diseases associated with abnormal activity of an ActRIIB protein and/or an ActRIIB ligand.
1. A variant ActRIIB protein consisting of the amino acid sequence of SEQ ID NO: 5.
2. The variant ActRIIB protein of claim 1 , wherein the protein is a homodimer.
3. A pharmaceutical preparation comprising the variant ActRIIB protein of claim 1 .
4. An isolated polynucleotide comprising a coding sequence for the variant ActRIIB protein of claim 1 .
5. The isolated polynucleotide of claim 4 , wherein the polynucleotide comprises the nucleic acid sequence of SEQ ID NO: 10.
6. A vector comprising the polynucleotide of claim 4 .
7. A cell comprising the polynucleotide of claim 4 , wherein the cell is not within a human.
8. A method of producing variant ActRIIB protein, the method comprising culturing the cell of claim 7 and expressing the variant ActRIIB protein.
9. The method of claim 8 , wherein the cell is a CHO cell.
10. The method of claim 8 , wherein the variant ActRIIB protein is expressed using a TPA leader sequence.
11. The method of claim 10 , wherein the TPA leader sequence comprises the amino acid sequence of SEQ ID NO: 8.