Regulation of human sphingosine kinase-like protein
OwnerSophia Kossida, Jeffrey Encinasinventors
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Abstract
Reagents which regulate human sphingosine kinase-like protein activity and reagents which bind to human sphingosine kinase-like gene products can be used to regulate intracellular signaling and consequently cell proliferation and apoptosis. Such regulation is particularly useful for treating cancer, allergies including but not limited to asthma, autoimmune diseases such as rheumatoid arthritis, and central and peripheral nervous system disorders, such as Parkinson's disease.
Claims65
A cDNA encoding a polypeptide comprising an amino acid sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof.
An expression vector comprising a polynucleotide which encodes a polypeptide comprising an amino acid sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof.
A host cell comprising an expression vector which encodes a polypeptide comprising an amino acid sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof.
A purified polypeptide comprising an amino acid sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof.
A fusion protein comprising a polypeptide consisting of an amino acid sequence selected from the group consisting of (a) the amino acid sequence shown in SEQ ID NOS:
- 2, 10, or 11 and (b) biologically active variants thereof.
A method of producing a polypeptide comprising an amino acid sequence selected from the group consisting of (a) an amino acid sequence selected from the group consisting of SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof, comprising the steps of:
- culturing a host cell comprising an expression vector that 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 an amino acid sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof, comprising the steps of:
- hybridizing a polynucleotide comprising 11 contiguous nucleotides selected from the group consisting of (a) the complement of a nucleotide sequence selected from the group consisting of SEQ ID NOS:
- 1 and 9, (b) a polynucleotide that hybridizes under stringent conditions to (a), (c) a polynucleotide having a nucleic acid sequence that deviates from the nucleic acid sequences specified in (a) and (c) due to the degeneration of the genetic code, and (d) a polynucleotide that represents a fragment, derivative, or allelic variation of a nucleic acid sequence specified in (a) to (c) to nucleic acid material of a biological sample to form a hybridization complex;
- and
- detecting the hybridization complex.
A method of detecting a polypeptide comprising an amino acid sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof, 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 that can regulate an activity of a human sphingosine kinase-like protein, comprising the steps of:
- contacting a test compound with a polypeptide comprising an amino acid sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof;
- and
- detecting binding of the test compound to the polypeptide, wherein a test compound that binds to the polypeptide is identified as a potential agent for regulating the activity of the human sphingosine kinase-like protein.
A method of screening for therapeutic agents that can regulate an enzymatic activity of a human sphingosine kinase-like protein, comprising the steps of:
- contacting a test compound with a polypeptide comprising an amino acid sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof;
- and
- detecting the enzymatic activity of the polypeptide, wherein a test compound that increases the enzymatic activity of the polypeptide is identified as a potential therapeutic agent for increasing the enzymatic activity of the human sphingosine kinase-like protein, and wherein a test compound that decreases the enzymatic activity of the polypeptide is identified as a potential therapeutic agent for decreasing the enzymatic activity of the human sphingosine kinase-like protein.
A method of screening for therapeutic agents that can regulate an activity of a human sphingosine kinase-like protein, comprising the steps of:
- contacting a test compound with a product encoded by a polynucleotide comprising a nucleotide sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof;
- and
- detecting binding of the test compound to the product, wherein a test compound that binds to the product is identified as a potential therapeutic agent for regulating the activity of the human sphingosine kinase-like protein.
A method of reducing an activity of a human sphingosine kinase-like protein, comprising the step of:
- contacting a cell comprising the human sphingosine kinase-like protein with a reagent that specifically binds to a product encoded by a polynucleotide comprising a nucleotide sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof, whereby the activity of the human sphingosine kinase-like protein is reduced.
A pharmaceutical composition, comprising:
- a reagent that specifically binds to a polypeptide comprising an amino acid sequence selected from the group consisting of (a) amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof;
- and
- a pharmaceutically acceptable carrier.
A pharmaceutical composition, comprising:
- a reagent that specifically binds to a product of a polynucleotide comprising a coding sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof;
- and
- a pharmaceutically acceptable carrier.
A pharmaceutical composition, comprising:
- an expression vector encoding a polypeptide comprising an amino acid sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof;
- and
- a pharmaceutically acceptable carrier.
A method of treating a disorder selected from the group consisting of a cancer, an allergy, a CNS disorder, and an autoimmune disease, comprising the step of:
- administering to a patient in need thereof a therapeutically effective dose of a reagent that inhibits a function of a human sphingosine kinase-like protein, wherein the human sphingosine kinase-like protein comprises an amino acid sequence selected from the group consisting of (a) the amino acid sequences shown in SEQ ID NOS:
- 2, 10, and 11 and (b) biologically active variants thereof, whereby symptoms of the disorder are ameliorated.
An isolated polynucleotide selected from the group consisting of:
- (a) a polynucleotide encoding a protein that comprises the amino acid sequence of SEQ ID NO:
- 2, 10, or 11, (b) a polynucleotide comprising a sequence selected from the group consisting of SEQ ID NOS:
- 1 and 9, (c) a polynucleotide which hybridizes under stringent conditions to a polynucleotide specified in (a) or (b);
- (d) a polynucleotide having a nucleic acid sequence that deviates from the nucleic acid sequences specified in (a)-(c) due to the degeneration of the genetic code, and (e) a polynucleotide that represents a fragment, derivative, or allelic variation of a nucleic acid sequence specified in (a)-(d).
A preparation of antibodies that specifically bind to a polypeptide selected from the group consisting of (a) the amino acid sequence shown in SEQ ID NO:
- 2, 10, or 11 and (b) biologically active variants thereof.
An antisense oligonucleotide that hybridizes to a polynucleotide selected from the group consisting of (a) a polynucleotide encoding a protein that comprises the amino acid sequence of SEQ ID NO:
- 2, 10, or 11, (b) a polynucleotide comprising a nucleotide sequence selected from the group consisting of SEQ ID NOS:
- 1 and 9, (c) a polynucleotide which hybridizes under stringent conditions to a polynucleotide specified in (a) or (b), (d) a polynucleotide having a nucleic acid sequence that deviates from the nucleic acid sequences specified in (a)-(c) due to the degeneration of the genetic code, and (e) a polynucleotide that represents a fragment, derivative, or allelic variation of a nucleic acid sequence specified in (a)-(d).
Dependencies are inferred from the claim text.