A tyrosine kinase physically associates with the β-subunit of the human IL-2 receptor

M. R. Fung, R. M. Scearce, J. A. Hoffman, N. J. Peffer, S. R. Hammes, J. B. Hosking, R. Schmandt, W. A. Kuziel, B. F. Haynes, Gordon Mills, W. C. Greene

Research output: Contribution to journalArticle

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Abstract

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 languageEnglish (US)
Pages (from-to)1253-1260
Number of pages8
JournalJournal of Immunology
Volume147
Issue number4
StatePublished - Jan 1 1991
Externally publishedYes

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Interleukin-2 Receptors
Protein-Tyrosine Kinases
Interleukin-2
Phosphorylation
Protein Kinases
Phosphotransferases
Growth
Threonine
Mitogens
Serine
Signal Transduction
Ligands
T-Lymphocytes
Amino Acids
Peptides
Antibodies
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology

Cite this

Fung, M. R., Scearce, R. M., Hoffman, J. A., Peffer, N. J., Hammes, S. R., Hosking, J. B., ... Greene, W. C. (1991). A tyrosine kinase physically associates with the β-subunit of the human IL-2 receptor. Journal of Immunology, 147(4), 1253-1260.

A tyrosine kinase physically associates with the β-subunit of the human IL-2 receptor. / Fung, M. R.; Scearce, R. M.; Hoffman, J. A.; Peffer, N. J.; Hammes, S. R.; Hosking, J. B.; Schmandt, R.; Kuziel, W. A.; Haynes, B. F.; Mills, Gordon; Greene, W. C.

In: Journal of Immunology, Vol. 147, No. 4, 01.01.1991, p. 1253-1260.

Research output: Contribution to journalArticle

Fung, MR, Scearce, RM, Hoffman, JA, Peffer, NJ, Hammes, SR, Hosking, JB, Schmandt, R, Kuziel, WA, Haynes, BF, Mills, G & Greene, WC 1991, 'A tyrosine kinase physically associates with the β-subunit of the human IL-2 receptor', Journal of Immunology, vol. 147, no. 4, pp. 1253-1260.
Fung MR, Scearce RM, Hoffman JA, Peffer NJ, Hammes SR, Hosking JB et al. A tyrosine kinase physically associates with the β-subunit of the human IL-2 receptor. Journal of Immunology. 1991 Jan 1;147(4):1253-1260.
Fung, M. R. ; Scearce, R. M. ; Hoffman, J. A. ; Peffer, N. J. ; Hammes, S. R. ; Hosking, J. B. ; Schmandt, R. ; Kuziel, W. A. ; Haynes, B. F. ; Mills, Gordon ; Greene, W. C. / A tyrosine kinase physically associates with the β-subunit of the human IL-2 receptor. In: Journal of Immunology. 1991 ; Vol. 147, No. 4. pp. 1253-1260.
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abstract = "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.",
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AU - Scearce, R. M.

AU - Hoffman, J. A.

AU - Peffer, N. J.

AU - Hammes, S. R.

AU - Hosking, J. B.

AU - Schmandt, R.

AU - Kuziel, W. A.

AU - Haynes, B. F.

AU - Mills, Gordon

AU - Greene, W. C.

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N2 - 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.

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