This invention provides an optical probe useful as an optical probe or senso r of post translational type modifications, such as phosphorylation. The invention comprises a polypeptide moiety, which contains a recognition motif for a post translational type activity, and a protease site, which is couple d to a probe moiety. Modification of the polypeptide, by the post translationa l type activity, results in a modulation of the rate at which a protease cleav es the polypeptide which is sensed by a measurable change in at least one optic al property of the optical probe upon cleavage. The present invention also includes a recombinant nucleic acid molecule that encodes an optical probe a nd a vector and host cell or library of cells that include the recombinant nucleic acid molecule. The optical probe can be used in methods to determine whether a sample, including a cell or a sample from an organism, contains a post-translational type modification activity. Such methods can also be used to determine whether a test chemical modulates the activity of a modifying activity, and thus can be used to identify therapeutic compositions. The identification of such therapeutic compositions can be automated using a system that includes an optical probe.
OPTICAL PROBES AND ASSAYS