30 results about "LRP6" patented technology

Monoclonal antibodies against LRP6 and that block the Wnt signaling pathway are disclosed. Methods of production and use thereof are also disclosed.

The invention provides a method for regulating a cellular pathway by using plant hormone ABA (Abscisic Acid) and a small molecular substance PYR (Pyrabactin). The method comprises the following steps:constructing ABA receptor proteins ABI1 and PYR1 in Arabidopsis thaliana on a human cell expression vector, then transferring into HEK293T cells respectively, adding ABA in order that the two receptor proteins undergo induced interaction, and adding a PYR inhibitor in order that the interaction degree is weakened; fusing other human cell signal pathway key proteins with the two receptor proteins,and making the two receptor proteins undergo interaction under the induction of the ABA, so that a fused signal pathway also undergoes ABA induced aggregation. According to the method provided by theinvention, a key protein LRP6 on a human Wnt pathway is selected. After fusion expression of an ABA receptor and LRP6, LRP6 aggregates under the induction of ABA, thereby promoting the production ofbeta-catenin and opening up an intracellular signal pathway. After the PYR inhibitor is added, the production amount of the beta-catenin is reduced, and the cellular pathway is closed.

The loss of the SOST gene product sclerostin leads to sclerosteosis characterized byihigh bone mass (HBM). In this report, we found that sclerostin could antagonize canonical, Wnt signaling in human embryonic kidney A293 cells and mouse osteoblastic MC3T3 cells. This sclerostin-mediated antagonism could be reversed by over-expression of Wnt coreceptor LRP5. In addition, we found that sclerostin bound to LRP5 as well as LRP6 and identified the first two YWTD-EGF repeat domains of LRP5 as being responsible for the binding. Although these two repeat domains are required for transducing canonical Wnt signals, canonical Wnt did not appear to compete with sclerostin for binding to LRP5. Examination of the expression of sclerostin and Wnt7b, an autocrine canonical Wnt, during primary calvarial osteoblast differentiation revealed that sclerostin is expressed at the late stages of osteoblast differentiation coinciding with the expression of osteogenic marker osteocalcin and trailing after the expression of Wnt7b. Given the plethora of evidence indicating that canonical Wnt signaling stimulates osteogenesis, we believe that the HBM phenotype associated with the loss of sclerostin may at least in part be attributed to an increase in canonical Wnt signaling resulting from the reduction in sclerostin-mediated Wnt antagonism.

The invention provides novel biparatopic LRP5 / LRP6 cross-reactive binding polypeptides, and more specifically novel biparatopic LRP5 / LRP6 cross-reactive immunoglobulin single variable domain constructs which can inhibit Wnt signaling pathways. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as cancer.