Regulation of human plc delta-1
AssigneeBayer Aktiengesellschaft
InventorYonghong Xiao
Life of this patent
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Abstract
Reagents which regulate human PLC delta-1 activity and reagents which bind to human PLC delta-1 gene products can be used, inter alia, to treat COPD, congestive heart failure, hypertension, and cancer, and a variety of conditions in which signal transduction is impaired.
Drawings
Claims75
An isolated polynucleotide encoding a PLC delta-1 polypeptide and being selected from the group consisting of:
- a) a polynucleotide encoding a PLC delta-1 polypeptide comprising an amino acid sequence selected form the group consisting of:
- amino acid sequences which are at least about 50% identical to the amino acid sequence shown in SEQ ID NO:
- 2;
- the amino acid sequence shown in SEQ ID NO:
- 2
- amino acid sequences which are at least about 50% identical to the amino acid sequence shown in SEQ ID NO:
- 4;
- the amino acid sequence shown in SEQ ID NO:
- 4;
- amino acid sequences which are at least about 50% identical to the amino acid sequence shown in SEQ ID NO:
- 9;
- the amino acid sequence shown in SEQ ID NO:
- 9;
- amino acid sequences which are at least about 50% identical to the amino acid sequence shown in SEQ ID NO:
- 13;
- and
- the amino acid sequence shown in SEQ ID NO:
- 13.
- b) a polynuecleotide comprising the sequence of SEQ ID NOS:
- 1, 3, 5, 6, 7, 8 or 10;
- c) a polynucleotide which hybridizes under stringent conditions to a polynucleotide specified in (a) and (b);
- d) a polynucleotide the sequence of which deviates from the polynucleotide sequences specified in (a) to (c) due to the degeneration of the genetic code;
- and
- e) a polynucleotide which represents a fragment, derivative or allelic variation of a polynucleotide sequence specified in (a to (d).
A cDNA encoding a polypeptide comprising the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13.
An expression vector comprising a polynucleotide which encodes a polypeptide comprising the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13.
A host cell comprising an expression vector which encodes a polypeptide comprising the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13.
A purified polypeptide comprising the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13.
A fusion protein comprising a polypeptide having the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13.
A method of producing a polypeptide comprising the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13, comprising the steps of:
- culturing a host cell comprising an expression vector which encodes the polypeptide under conditions whereby the polypeptide is expressed;
- and isolating the polypeptide.
A method of detecting a coding sequence for a polypeptide comprising the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13, comprising the steps of:
- hybridizing a polynucleotide comprising 11 contiguous nucleotides of SEQ ID NO:1, 3, 5, 6, 7, 8 or 10 to nucleic acid material of a biological sample, thereby forming a hybridization complex;
- and detecting the hybridization complex.
A method of detecting a polypeptide comprising the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13, comprising the steps of:
- contacting a biological sample with a reagent that specifically binds to the polypeptide to form a reagent-polypeptide complex;
- and detecting the reagent-polypeptide complex.
A method of screening for agents which can modulate the activity of a human PLC delta-1, comprising the steps of:
- contacting a test compound with a polypeptide comprising an amino acid sequence selected from the group consisting of:
- (1) amino acid sequences which are at least about 50% identical to the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13 and (2) the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13;
- and
- detecting binding of the test compound to the polypeptide, wherein a test compound which binds to the polypeptide is identified as a potential agent for regulating activity of the human PLC delta-1.
A method of screening for agents which modulate an activity of a human PLC delta-1, comprising the steps of:
- contacting a test compound with a polypeptide comprising an amino acid sequence selected from the group consisting of:
- (1) amino acid sequences which are at least about 50% identical to the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13 and (2) the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13;
- and
- detecting an activity of the polypeptide, wherein a test compound which increases the activity of the polypeptide is identified as a potential agent for increasing the activity of the human PLC delta-1, and wherein a test compound which decreases the activity of the polypeptide is identified as a potential agent for decreasing the activity of the human PLC delta-1.
A method of-screening for agents which modulate an activity of a human PLC delta-1, comprising the steps of:
- contacting a test compound with a product encoded by a polynucleotide which comprises the nucleotide sequence shown in SEQ ID NO:1, 3, 5, 6, 7, 8 or 10;
- and
- detecting binding of the test compound to the product, wherein a test compound which binds to the product is identified as a potential agent for regulating the activity of the human PLC delta-1.
A method of reducing activity of a human PLC delta-1, comprising the step of:
- contacting a cell with a reagent which specifically binds to a product encoded by a polynucleotide comprising the nucleotide sequence shown in SEQ ID NO:
- 1, 3, 5, 6, 7, 8 or 10, whereby the activity of a human PLC delta-1 is reduced.
A pharmaceutical composition, comprising:
- a reagent which specifically binds to a polypeptide comprising the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13;
- and a pharmaceutically acceptable carrier.
A pharmaceutical composition, comprising:
- a reagent which specifically binds to a product of a polynucleotide comprising the nucleotide sequence shown in SEQ ID NO:1, 3, 5, 6, 7, 8 or 10;
- and a pharmaceutically acceptable carrier.
A pharmaceutical composition, comprising:
- an expression vector encoding a polypeptide comprising the amino acid sequence shown in SEQ ID NO:2, 4, 9 or 13;
- and a pharmaceutically acceptable carrier.
A method of treating a PLC delta-1 dysfunction related disease, comprising the step of:
- administering to a patient in need thereof a therapeutically effective dose of a reagent that modulates a function of a human PLC delta-1, whereby symptoms of the PLC delta-1 dysfunction related disease are ameliorated.
Dependencies are inferred from the claim text.