Receptor-Ligand Assay for orphan tyrosine kinase receptors

Summary Transmembrane receptors are proteins which are localized in the plasma membrane of eukaryotic cells. They mediate molecular signaling functions by binding specifically with an external signaling molecule (the ligand) which activates the receptor. Receptor activation in turn leads to an intracellular catalytic function mediated by an intracellular domain of the transmembrane receptor, while the ligand remains outside the cell.

Researchers have found it relatively straightforward to isolate novel receptors, since receptors often share homologous sequences, especially in the catalytic domain. Identification of, and isolation of, the ligands for these newly discovered receptors is much more difficult. As a result, many newly discovered receptors have no known ligand, and are characterized as orphan receptors.

Harvard Medical School researchers have developed and patented a novel approach for the identification and isolation of transmembrane receptors and their ligands which is especially useful for the discovery of ligands to orphan receptors. The system is based on the observation that the functional expression of a heterologous tyrosine kinase receptor and its corresponding polypeptide ligand in yeast leads to activation of the receptor and an increase in intracellular tyrosine phosphorylation.

Applications APPLICATION:

- The discovery of ligands for orphan tyrosine kinase receptors.

ADVANTAGES:

- System works with almost all genes, in a system whose molecular biology is well understood

- System has low endogenous tyrosine kinase activity, leading to low backgrounds and sensitive dection.

- The system can identify polypeptide ligands for orphan receptors. For Further Information Please Contact the Director of Business Development inger Email: michal_preminger@hms.harvard.edu Telephone: (617) 432-0920

Inventor(s): Kirschner, Marc W.

Type of Offer: Licensing



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