Compositions for diagnosis and therapy of diseases associated with aberrant expression of futrins (R-spondins) and/or Wnt
The present invention relates to a composition useful for the diagnosis of diseases associated with aberrant expression of the genes encoding the secreted proteins Futrin 1, 2, 3 and/or 4(=R-Spondin 2, 3, 1 and 4, respectively), e.g. in connection with tumors or diseases of the muscle, kidneys or bones. The present invention also relates to a pharmaceutical composition containing a compound which is capable of modifying (a) the expression of the gene encoding Futrin 1, 2, 3 and/or 4 or (b) the activity of the Futrin 1, 2, 3 and/or 4 protein.
1. A method of determining whether a binding partner of a Futrin 2 polypeptide affects Wnt signaling activity, the method comprising:
(a) providing a mammalian cell in culture comprising the Futrin 2 polypeptide and a Wnt inducible reporter, wherein the Futrin 2 polypeptide comprises the amino acid sequence of SEQ ID NO:27, the amino acid sequence of amino acids 21-272 of SEQ ID NO:27, the amino acid sequence of amino acids 1-149 of SEQ ID NO:27, or the amino acid sequence of amino acids 21-149 of SEQ ID NO:27, wherein the Futrin 2 polypeptide is able to promote Wnt signaling; and
(b) detecting the level of reporter expression in the cell in the presence and absence of the binding partner, wherein a change in the level of reporter expression indicates that the binding partner affects the Wnt signaling.
2. The method of claim 1 , wherein the change is a decrease in the level of reporter expression and the decrease indicates that the binding partner is an antagonist of Wnt signaling.
3. The method of claim 2 , wherein the binding partner is an antibody.
4. The method of claim 3 , wherein the antibody is a monoclonal antibody.
5. The method of claim 1 , wherein the Futrin 2 polypeptide comprises the amino acid sequence of amino acids 21-149 of SEQ ID NO:27.
6. The method of claim 5 , wherein the Futrin 2 polypeptide comprises the amino acid sequence of amino acids 21-272 of SEQ ID NO:27.
7. The method of claim 5 , wherein the Futrin 2 polypeptide comprises SEQ ID NO:27.
8. The method of claim 5 , wherein the Futrin 2 polypeptide comprises the amino acid sequence of amino acids 1-149 of SEQ ID NO:27.
9. The method of claim 8 , wherein the functional fragment comprises the amino acid sequence of amino acids 21-149 of SEQ ID NO:27.
10. The method of claim 1 , wherein the change is an increase in the level of reporter expression and the increase indicates that the binding partner is an agonist of Wnt signaling.
11. The method of claim 1 , wherein the Futrin 2 polypeptide comprises the amino acid sequence of amino acids 21-272 of SEQ ID NO:27.
12. The method of claim 1 , wherein the Futrin 2 polypeptide comprises SEQ ID NO:27.
13. The method of claim 9 , wherein the Futrin 2 polypeptide comprises the amino acid sequence of amino acids 21-149 of SEQ ID NO:27.
14. The method of claim 13 , wherein the functional fragment comprises the amino acid sequence of amino acids 21-149 of SEQ ID NO:27.