The molecular basis for the generation of the human soluble interleukin 2 receptor.
Using an enzyme-linked immunosorbent assay (ELISA) employing two monoclonal antibodies recognizing distinct epitopes on the interleukin 2 receptor (IL2R) alpha chain (Tac molecule), we previously demonstrated that activated lymphocytes release a soluble interleukin 2 receptor molecule (sIL2R) in vitro and in vivo. The sIL2R is biochemically and structurally related to Tac, but its precise origin and functional role remain to be defined. We report here that a single IL2R cDNA is sufficient to direct the synthesis of both cell-associated and soluble released IL2R molecules. Northern analysis of IL2R cDNA transfected L-cell lines revealed the presence of mRNA species unaccounted for by known transcription termination or internal splice sites. Nevertheless, S1 nuclease digestion studies failed to detect alternately spliced mRNA transcripts that specifically lack transmembrane or cytoplasmic domains and which may encode a secreted IL2R molecule. Therefore sIL2R does not appear to be the product of a unique post-transcriptional splicing event. In the absence of any post-translational modifications, sIL2R is most likely generated by enzymatic cleavage and release of cell surface Tac. This proteolytic release of Tac may be but one example of a common cellular mechanism for regulating the membrane expression of cell surface molecules.
Rubin
L A
LA
Department of Medicine, University of Toronto, Ontario, Canada.
Galli
F
F
Greene
W C
WC
Nelson
D L
DL
Jay
G
G
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007739:L Cells / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D007376:Interleukin-2; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2