Insulin-like growth factor signaling and integrin
View Patent ↗Interaction between insulin-like growth factor 1 (IGFI) and integrin is involved in integrin-mediated cellular signaling, such as enhanced proliferation of cells expressing integrins, especially integrin alpha v beta 3, alpha 6 beta. 1 and alpha 6. beta. 4. A method for inhibiting integrin signaling by using an inhibitor of IGFI-integrin binding is disclosed A method for identifying inhibitors of IGFI-integrin binding is also described. Further disclosed are polypeptides, nucleic acids, and corresponding compositions for inhibiting integrin signaling.
1. An isolated polypeptide comprising the amino acid sequence of SEQ ID NO:1, with both of the Arg residues at positions 36 and 37 of SEQ ID NO:1 substituted with Glu, or with the Arg residue at position 50 of SEQ ID NO:1 is substituted with Glu.
2. A composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable excipient.
3. The composition of claim 2 , wherein the polypeptide is IGF1 mutant R36E/R37E.
4. The composition of claim 2 , wherein the polypeptide is IGF1 mutant R50E.
5. A kit for inhibiting IGF1 signaling, comprising the composition of claim 2 .
6. A method for inhibiting IGF1 signaling in a cell, comprising the step of contacting the cell with an effective amount of the polypeptide of claim 1 .
7. The method of claim 6 , wherein the inhibitor is IGF1 mutant R36E/R37E.
8. The method of claim 6 , wherein the inhibitor is IGF1 mutant R50E.
9. The method of claim 6 , wherein the cell is within a patient's body.
10. The method of claim 9 , wherein the contacting step is performed by intravenous, intraperitoneal, or intratumor injection.