Interleukin 4 signals through two related pathways

Alessandra Pernis, Bruce Witthuhn, Achsah D. Keegan, Keats Nelms, Evan Garfein, James N. Ihle, William E. Paul, Jacalyn H. Pierce, Paul Rothman

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

The interleukin 4 (IL-4) signaling pathway involves activation, by tyrosine phosphorylation, of two distinct substrates, a signal-transducing factor (STF-IL4) and the IL-4-induced phosphotyrosine substrate (4PS). It is not known whether the IL-4-mediated activation of these substrates occurs via related or distinct signaling pathways. We report that 32D cells, an IL-3- dependent myeloid progenitor cell line in which no phosphorylated 4PS is found, activate high levels of STF-IL4 in response to IL-4. Consistent with the known requirement for 4PS or insulin receptor substrate 1 (IRS-1) in IL- 4-mediated mitogenesis, activation of STF-IL4 in 32D cells is not sufficient for IL-4-inducible c-myc expression. In addition, we have examined the ability of 32D cells transfected with different truncation mutants of the human IL-4 receptor to activate Jak-3 kinase and STF-IL4 in response to human IL-4. As in the case of 4PS/IRS-1, we have found that activation of both Jak- 3 and STF-IL4 requires the presence of the IL-4 receptor region comprising aa 437-557. The finding that the same region of the IL-4 receptor is required for the induction of both 4PS/IRS-1 and STF-IL4 suggests that the IL-4- stimulated activation of these two substrates might involve common factors.

Original languageEnglish (US)
Pages (from-to)7971-7975
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number17
DOIs
StatePublished - Aug 15 1995
Externally publishedYes

Keywords

  • Janus kinases
  • cytokine
  • signal transducers and activators of transcription

ASJC Scopus subject areas

  • General

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    Pernis, A., Witthuhn, B., Keegan, A. D., Nelms, K., Garfein, E., Ihle, J. N., Paul, W. E., Pierce, J. H., & Rothman, P. (1995). Interleukin 4 signals through two related pathways. Proceedings of the National Academy of Sciences of the United States of America, 92(17), 7971-7975. https://doi.org/10.1073/pnas.92.17.7971