摘要:
Methods are provided for identifying agents which modulate the interaction of tyrosine kinases of the Syk family with integrins. Also provided are compositions and methods for using these agents to modulate tyrosine kinases of the Syk family and to treat disease such as thrombosis, inflammation, metastasis and tumor cell growth in a subject.
摘要:
The present invention provides a method for identifying an agent to be tested for an ability to treat a psychotic disorder in a patient in need of such treatment. The invention provides a method for screening candidate drugs for anti-psychotic drug activity, preferably atypical anti-psychotic activity, comprising contacting cells or tissues with a candidate drug, determining levels of phosphorylation of the intracellular signaling proteins, DARPP-32, ERK1, ERK2 and CREB, in said cells or tissues and determining the pattern of the levels of phosphorylation of the proteins. The pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB is, in certain embodiments, compared with the pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB in the presence of an atypical anti-psychotic drug.
摘要:
The invention provides an isolated polypeptide, or a fragment thereof, comprising a coiled-coil and an engineered site sufficient for the addition of a nullmoietynull, i.e., a group, that is one or more of a phosphate, ubiquitin, glycosyl or ADP-ribosyl moiety, wherein the polypeptide binds to a binding partner in a phosphorylation-, ubiquitination-, glycosylation- or ADP-ribosylation-dependent manner. The invention also relates to methods and kits utilizing an isolated polypeptide and its binding partner, which methods and kits permit monitoring of addition or removal of the one or more moieties.
摘要:
A molecule suitable for use as an indicator of free iron levels in a biological sample, the molecule including an iron binding moeity and a signal generating moeity, wherein an intensity of the signal generated by the signal generating moeity is related to an amount of the iron bound by the iron binding moeity.
摘要:
The present invention relates to in vitro and ex vivo methods of screening for modulators, homologues, and mimetics of lethal factor mitogen activated protein kinase kinase (MAPKK) protease activity, as well as methods of treating cancer by administering LF to transformed cells.
摘要:
A method for measuring the activity of dual substrate enzymes and for identifying compounds that modulate the activity of dual substrate enzymes comprising first substrate, a macromolecule that is enzymatically modified with a radioactively-labeled portion of the second substrate, said method comprising: a. adding a capture resin to a buffered mixture of an enzyme, allowing the enzyme to catalyze transfer of the radiolabeled portion of the radiolabeled second substrate to the non-radiolabeled first substrate, radiolabeled first substrate, and a radiolabeled second substrate in the presence or absence of a test compound; b. removing unreacted radiolabeled second substrate; c. adding a scintillant resin to the enzyme-radiolabeled first substrate mixture; and d. measuring the amount of radiolabeled first substrate by scintillation counting, measuring the amount of radiolabeled first substrate by scintillation counting, and comparing the two measurements.
摘要:
The invention relates to methods for detecting the cytotoxic activity of an effector, such as a cytotoxic T lymphocyte, on a non-microbial target cell. Detection of cytotoxic activity is preferably achieved by detecting adenylate kinase release using photometric methods.
摘要:
The present invention relates to novel methods for identifying antiviral agents which selectively interfere with viral proteins that override the interferon(IFN)-induced cellular defense mechanisms against viral infection. In particular, the present- invention relates to screening assays that identify agents which selectively inhibit the interaction between viral proteins containing an interferon sensitivity determining region (ISDR) and IFN-induced PKR protein kinase. The present invention more particularly relates to screening assays that identify agents which selectively inhibit the interaction between hepatitis C virus (HCV) nonstructural 5A protein (NS5A), which contains an ISDR, and IFN-induced PKR protein kinase. The interaction between the viral ISDR and IFN-induced PKR protein kinase results in the override of IFN-induced cellular defense mechanisms to combat viral infection. Therefore the agents identified using the assays of the invention may have utility as antiviral agents.
摘要:
Disclosed herein are compositions and methods which are useful in the identification and isolation of components involved in transmembrane receptor-mediated signaling. Such components include the receptors themselves (e.g., tyrosine kinase receptors, cytokine receptors and tyrosine phosphatase receptors), as well as ligands which bind the receptors and modulators of the downstream intracellular catalytic event which characterizes receptor-mediated signalling. Two novel ligands for the FGF receptor and the nucleotide sequences encoding them are also described.
摘要:
This invention provides assays for protein kinase activity using fluorescent proteins engineered to include sequences that can be phosphorylated by protein kinases. The proteins exhibit different fluorescent properties in the non-phosphorylated and phosphorylated states.