Target of the phosphoinositide 3-kinase pathway
AssigneeThe Regents of the University of California
InventorPradipta Ghosh
Life of this patent
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Abstract
The present disclosure generally relates to tyrosine phosphorylation sites of an Akt enhancer, and methods for the detection of the phosphorylated tyrosine residues. In particular, anti-phosphotyrosine antibodies and binding proteins find use in the compositions and methods of the present disclosure.
Claims25
A method for assessing risk of metastasis of a solid tumor, the method comprising:
- a) subjecting a sample from the solid tumor to a procedure for quantitation of tyrosine phosphorylation of human Galpha-interacting protein (GIV);
- and
- b) detecting an elevated level of tyrosine phosphorylation of GIV in the sample as compared to a control sample, wherein the elevated level of tyrosine phosphorylation is associated with mestastasis or an increased risk of metastasis, and wherein the tyrosine phosphorylation of GIV comprises phosphorylation of one or both Y1764 and Y1798 of GIV.
An isolated antibody that binds specifically to a polypeptide comprising the phosphorylated amino acid sequence of SEQ ID NO:5 (pYFISS) or the phosphorylated amino acid sequence of SEQ ID NO:6 (pYATLP).
A method of screening for inhibitors of PI3K-GIV association, the method comprising:
- a) providing a first protein comprising one or both of the phosphorylated amino acid sequence of SEQ ID NO:5 (pYFISS), and the phosphorylated amino acid sequence of SEQ ID NO:6 (pYATLP);
- b) providing a second protein comprising an SH2 domain of p85alpha(PI3K);
- c) contacting the first protein to the second protein in the presence and absence of a test compound;
- d) measuring the level of binding of the first protein to the second protein;
- e) detecting a reduction in binding of the first protein to the second protein in the presence of the test compound as compared to the absence of the test compound, wherein the reduction in binding in the presence of the test compound indicates that the test compound is an inhibitor of PI3K-GIV association.
Dependencies are inferred from the claim text.