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| FUNCTIONAL-CHARACTERIZATION OF THE HUMAN INTERLEUKIN-15 RECEPTOR-ALPHA CHAIN AND CLOSE LINKAGE OF IL15RA AND IL2RA GENES |
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| Author(s): ANDERSON DM, KUMAKI S, AHDIEH M, BERTLES J, TOMETSKO M, LOOMIS A, GIRI J, COPELAND NG, GILBERT DJ, JENKINS NA, VALENTINE V, SHAPIRO DN, MORRIS SW, PARK LS, COSMAN D |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 270 Issue: 50 Pages: 29862-29869 Published: DEC 15 1995 |
| Times Cited: 222 References: 48 |
| Abstract: Interleukins-2 and -15 (IL-2 and IL-15) are cytokines with overlapping but distinct biological effects. Their receptors share two subunits (the IL-2R beta and -gamma chains) that are essential for signal transduction. The IL-2 receptor requires an additional IL-2-specific alpha subunit for high affinity IL-2 binding, Recently, a murine IL-15-specific alpha subunit was identified, cloned, and shown to be structurally related to IL-2R alpha. However, the murine IL-15R alpha alone bound IL-15 with a 1000-fold higher affinity than that seen with IL-2R alpha and IL-2. We now extend these studies into the human system with the isolation of three differentially spliced human IL-15R alpha variants that are all capable of high affinity binding of IL-15. The cytoplasmic domain of IL-15R alpha, like that of IL-2R alpha, is dispensable for mitogenic signaling, suggesting that the primary role of the alpha chains is to confer high affinity binding. At high concentrations, IL-15, like P2, is able to signal through a complex of IL-2R beta and -gamma in the absence of the cu subunit. Furthermore, the IL15RA and IL2RA genes have a similar intron-exon organization and are closely linked in both human and murine genomes. However, the distribution of expression of the lL-15R alpha is much wider than that of the IL-2R alpha, suggesting a broader range of cellular targets for IL-15. |
| Document Type: Article |
| Language: English |
| Reprint Address: ANDERSON, DM (reprint author), IMMUNEX RES & DEV CORP, DEPT MOLEC BIOL, 51 UNIV ST, SEATTLE, WA 98101 USA |
Addresses:
1. IMMUNEX RES & DEV CORP, DEPT BIOCHEM, SEATTLE, WA 98101 USA
2. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA
3. ST JUDE CHILDRENS HOSP, DEPT EXPTL ONCOL, MEMPHIS, TN 38101 USA
4. ST JUDE CHILDRENS HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38101 USA
5. UNIV TENNESSEE, COLL MED, DEPT PEDIAT, MEMPHIS, TN 38163 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: TK380 |
| ISSN: 0021-9258 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |