Cell surface expression of the high affinity IL-2R regulates, in part, the proliferative response occurring in Ag- or mitogen-activated T cells. The functional high affinity IL-2R is composed of at least two distinct ligand-binding components, IL-2Rα (Tac, p55) and IL-2Rβ (p70/75). The IL-2Rβ polypeptide appears to be essential for growth signal transduction, whereas the IL-2Rα protein participates in the regulation of receptor affinity. We have prepared and characterized two mAb, DU-1 and DU-2, that specifically react with IL-2Rβ. In vitro kinase assays performed with DU-2 immunoprecipitates, but not anti-IL-2Rα or control antibody immunoprecipitates, have revealed co-precipitation of a tyrosine kinase enzymatic activity that mediates phosphorylation of IL-2Rβ. Because both IL-2Rα and IL-2Rβ lack tyrosine kinase enzymatic domains, these findings strongly suggest the noncovalent association of a tyrosine kinase with the high affinity IL-2R complex. Deletion mutants of the intracellular region of IL-2Rβ, lacking either a previously described 'critical domain' between amino acids 267 and 322 or the carboxyl-terminal 198 residues (IL-2Rβ88), lacked the ability to co-precipitate this tyrosine kinase activity, as measured by phosphorylation of IL-2Rβ in vitro. Both of these mutants also failed to transduce growth-promoting signals in response to IL-2 in vivo. Analysis of the IL-2Rβ88 mutant receptor suggested that a second protein kinase mediating phosphorylation on serine and threonine residues physically interacts with the carboxyl terminus of IL-2Rβ. This kinase may be necessary but, alone, appears to be insufficient to support a full IL-2-induced proliferative response. These studies highlight the physical association of protein kinases with the cytoplasmic domain of IL-2Rβ and their likely role in IL-2-induced growth signaling mediated through the multimeric high affinity IL-2R complex.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Immunology|
|State||Published - 1991|
ASJC Scopus subject areas
- Immunology and Allergy