Class II cytokine receptor-7

#Cytokines are soluble proteins that influence the growth and differentiation of many cell types. Their receptors are composed of one or more integral membrane proteins that bind the cytokine with high affinity and transduce this binding event to the cell through the cytoplasmic portions of the certain receptor subunits. Cytokine receptors have been grouped into several classes on the basis of similarities in their extracellular ligand binding domains. For example, the receptor chains responsible for binding and/or transducing the effect of interferons (IFNs) are members of the type IIcytokine receptor family (CRF2), based upon a characteristic 200 residue extracellular domain. The demonstrated in vivo activities of these interferons illustrate the enormous clinical potential of, and need for, other cytokines, cytokine agonists, and cytokine antagonists.

#The present invention fills this need by providing novel cytokine receptors and related compositions and methods. In particular, the present invention provides for an extracellular ligand-binding region of a mammalian Zcytor7 receptor, alternatively also containing either a transmembrane domain or both an intracellular domain and a transmembrane domain.

#Within one aspect, the present invention provides an isolated polynucleotide encoding a ligand-binding receptor polypeptide. The polypeptide comprises a sequence of amino acids selected from the group consisting of (a) residues 30 through 250 of SEQ ID NO:2; (b) allelic variants of (a); and (c) sequences that are at least 80% identical to (a) or (b). Within one embodiment, the polypeptide comprises residues 30 through 250 of SEQ ID NO:2. Within another embodiment, the polypeptide encoded by the isolated polynucleotide further comprises a transmembrane domain. The transmembrane domain may comprise residues 251 through 274 of SEQ ID NO:2, or an allelic variant thereof. Within another embodiment, the polypeptide encoded by the isolated polynucleotide further comprises an intracellular domain, such as an intracellular domain comprising residues 275 through 553 of SEQ ID NO:2, or an allelic variant thereof. Within further embodiments, the polynucleotide encodes a polypeptide that comprises residues 1 through 553, 1 through 274, 1 through 250, 30 through 274 or 30 through 553 of SEQ ID NO:2. Within an additional embodiment, the polypeptide further comprises an affinity tag. Within a further embodiment, the polynucleotide is DNA. Also claimed are the isolated polypeptides encoded by these polynucleotides.

#The invention is further illustrated by the following non-limiting examples.

#Expressed sequence tag (EST) 277139 (SEQ ID NO:3) was identified. The cDNA clone (ID No. 50416) was obtained from the IMAGE consortium Lawrence Livermore National Laboratory through Genome Systems, Inc. The cDNA was supplied as an agar stab containing E. coli transfected with a plasmid having the cDNA of interest. The E. coli was streaked on an agar plate. The plasmid was designated pSL7139. The cDNA insert in plasmid pSL7139 was sequenced. The insert was determined to be 1231 bp in length, but was not a full length sequence.

#A human testis cDNA template was made using a MARATHON™ cDNA Amplification Kit (Clontech Laboratories, Inc., Palo Alto, Calif.) according to the supplier s instructions. A 5 RACE reaction was used to obtain a full-length cDNA. The RACE reaction was carried out in two reactions employing two sets of primers. Reaction I (outer nest), using primers ZC11,107 (SEQ ID NO:4) and AP-1 (SEQ ID NO: 5) (Clontech Laboratories) was run for 35 cycles at 98° C. for 20 seconds, 45° C. for 20 seconds; 68° for 4 minutes and a final extension time of 10 minutes at 68° C. One μl of a 1:100 dilution of the reaction product was used as a template in reaction II (inner nest). Primers were ZC11,108 (SEQ ID NO:6) and AP-2 (SEQ ID NO:7) (Clontech Laboratories). The reaction was run at 98° C. for 30 seconds, and 30 cycles each cycle being comprised of 98° C. for 28 seconds; 43° C. for 20 seconds; and 68° C. for 3.5 minutes with a final extension at 68° C. for 10 minutes.