DSP-9 dual-specificity phosphatase
AssigneeCEPTYR, Inc.
InventorsRalf M. Luche, Bo Wei
Life of this patent
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Abstract
Compositions and methods are provided for the treatment of conditions associated with cell proliferation, cell differentiation and cell survival. In particular, the dual-specificity phosphatase DSP-9, and polypeptide variants thereof that stimulate dephosphorylation of DSP-9 substrates, are provided. The polypeptides may be used, for example, to identify antibodies and other agents that inhibit DSP-9 activity. The polypeptides and agents may be used to modulate cell proliferation, differentiation and survival.
Claims49
An isolated polypeptide having the sequence of DSP-9 recited in SEQ ID NO:2, or a variant thereof that differs in one or more amino acid deletions, additions, insertions or substitutions at no more than 50% of the residues in SEQ ID NO:2, such that the polypeptide retains the ability to dephosphorylate an activated MAP-kinase.
An isolated polynucleotide that encodes at least ten consecutive amino acids of a polypeptide having a sequence corresponding to SEQ ID NO:2.
An isolated polynucleotide that encodes at least fifteen consecutive amino acids of a polypeptide having a sequence corresponding to SEQ ID NO:2.
An isolated polynucleotide that detectably hybridizes to the complement of the sequence recited in SEQ ID NO:
- 1 under conditions that include a wash in 0.1×SSC and 0.1% SDS at 50° C. for 15 minutes.
An isolated antibody, or antigen binding fragment thereof, that specifically binds to a DSP-9 polypeptide having the sequence of SEQ ID NO:2.
A method for screening for an agent that modulates DSP-9 activity, comprising the steps of:
- (a) contacting a candidate agent with a cell comprising a DSP-9 promoter operably linked to a polynucleotide encoding a detectable transcript or protein, under conditions and for a time sufficient to permit interaction between the promoter and candidate agent;
- and
- (b) subsequently evaluating the expression of the polynucleotide, relative to a predetermined level of expression in the absence of candidate agent;
- and therefrom identifying an agent that modulates DSP-9 activity.
A method for modulating a proliferative response in a cell, comprising contacting a cell with an agent that modulates DSP-9 activity.
A method for modulating differentiation of a cell, comprising contacting a cell with an agent that modulates DSP-9 activity.
A method for modulating survival of a cell, comprising contacting a cell with an agent that modulates DSP-9 activity.
A method for treating a patient afflicted with a disorder associated with DSP-9 activity, comprising administering to a patient a therapeutically effective amount of an agent that modulates DSP-9 activity.
A DSP-9 substrate trapping mutant polypeptide that differs from the sequence recited in SEQ ID NO:2 in one or more amino acid deletions, additions, insertions or substitutions at no more than 50% of the residues in SEQ ID NO:2, such that the polypeptide binds to a substrate with an affinity that is not substantially diminished relative to DSP-9, and such that the ability of the polypeptide to dephosphorylate a substrate is reduced relative to DSP-9.
Dependencies are inferred from the claim text.