SM38 nucleic acid molecules
The present invention relates to methods for modulating the migratory activity of cells expressing CD38 for the treatment of disorders including, but not limited to, inflammation, ischemia, asthma, autoimmune disease, diabetes, arthritis, allergies, infection with pathogenic organisms, such as parasites, and transplant rejection. Such cells include, for example, neutrophils, lymphocytes, eosinophils, macrophages and dentritic cells. The invention further relates to drug screening assays designed to identify compounds that modulate the ADP-ribosyl cyclase activity of CD38 and the use of such compounds in the treatment of disorders involving CD38 modulated cell migration. Additionally, the invention relates to the isolation and characterization of a CD38 homologue from the parasitic flatworm, Schistosoma mansoni.
1. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes the SM38 amino acid sequence of FIG. 13A (SEQ ID NO: 5).
2. The isolated nucleic acid molecule of claim 1 comprising the SM38 nucleic acid sequence of FIG. 13A (SEQ ID NO: 1).
3. An isolated nucleic acid molecule comprising a nucleotide sequence that hybridizes over the full length to the nucleotide sequence of claim 2 in 0.5 M NaHPO 4 , 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C., and washing in 0.1×SSC/0.1% SDS at 68° C.
4. An isolated nucleic acid molecule comprising a nucleotide sequence that hybridizes over the full length to the plasmid pCR2.1-TOPO:SM38 5-18 (ATCC Deposit No: PTA-3780), or plasmid SK:SM38LC12 (ATCC Deposit No:PTA3781), in 0.5 M NaHPO 4 , 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C., and washing in 0.1×SSC/0.1% SDS at 68° C.
5. A recombinant expression vector comprising the nucleic acid molecule of claims 1 - 3 or 4 .
6. A recombinant cell comprising the nucleic acid molecule of claims 1 - 3 or 4 .
7. A method of producing a SM38 protein comprising growing a recombinant cell comprising the nucleic acid molecule of claims 1 - 3 or 4 such that the encoded SM38 protein is expressed by the cell and recovering the expressed SM38 protein (SEQ ID NO: 5).