Structure-function relationships for the IL 2-receptor system. IV. Analysis of the sequence and ligand-binding properties of soluble Tac protein.
The Tac protein is one of at least two glycoproteins known to bind the growth and differentiation factor interleukin 2 (IL 2). In addition to its location on the cell surface, where it plays a part in high and low affinity IL 2 receptors, Tac is released from activated lymphocytes in a soluble form. We observed this release both for Tac protein labeled biosynthetically and for Tac protein labeled by surface iodination of intact cells. Competitive binding studies indicated that the soluble Tac protein retained an ability to bind IL 2 with a low affinity (Kd of 11.1 nM). In addition, structural analysis revealed that the polypeptide chain began at position 1 and ended at or just before Cys-192 of the full-length molecule. Thus, the protein was missing its normal transmembrane and intracytoplasmic segments, accounting for its solubility and cellular release. The apparent lack of modification in the amino acid sequence and the termination at Cys-192 are inconsistent with a mechanism of cellular release dependent only on alternate mRNA splicing. Instead, the results suggest that proteolysis may accompany the release of soluble Tac protein from cells expressing IL 2 receptors.
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000378:metabolism*; D001667:Binding, Competitive; D002460:Cell Line; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009182:Mycosis Fungoides / Q000473:pathology; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism*; D015375:Receptors, Interleukin-2; D012995:Solubility; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000954:Antigens, Surface; D006023:Glycoproteins; D007376:Interleukin-2; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7