The insulin receptor substrate-1-related 4PS substrate but not the interleukin-2Rγ chain is involved in interleukin-13-mediated signal transduction

L. M. Wang, P. Michieli, W. R. Lie, F. Liu, C. C. Lee, A. Minty, X. J. Sun -, A. Levine, M. F. White, J. H. Pierce

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin-13 (IL-13) induced a potent mitogenic response in IL-3- dependent TF-1 cells and DNA synthesis to a lesser extent in MO7E and FDC-P1 cells. IL-13 stimulation of these lines, like IL-4 and insulin-like growth factor-1 (IGF-1), resulted in tyrosine phosphorylation of a 170-kD substrate. The tyrosine-phosphorylated 170-kD substrate strongly associated with the 85- kD subunit of phosphoinositol-3 (PI-3) kinase and with Grb-2. Anti-4PS serum readily detected the 170-kD substrate in lysates from both TF-1 and FDC-P1 cells stimulated with IL-13 or IL-4. These data provide evidence that IL-13 induces tyrosine phosphorylation of the 4PS substrate, providing an essential interface between the IL-13 receptor and signaling molecules containing SH2 domains. IL-13 and IL-4 stimulation of murine L cell fibroblasts, which endogenously express the IL-4 receptor (IL-4Rα) and lack expression of the IL-2 receptor γ subunit (IL-2Rγ), resulted in tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1)/4PS. Enhanced tyrosine phosphorylation of IRS-1/4PS was observed in response to IL-4, but not IL-13 treatment of L cells transfected with the IL-2Rγ chain. These results indicate that IL-13 does not use the IL-2Rγ subunit in its receptor complex and that expression of IL-2Rγ enhances, but is not absolutely required for mediating IL-4- induced tyrosine phosphorylation of IRS-1/4PS.

Original languageEnglish
Pages (from-to)4218-4227
Number of pages10
JournalBlood
Volume86
Issue number11
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Hematology

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