Interleukin 4 signals through two related pathways

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

Research output: Contribution to journalArticle

79 Citations (Scopus)

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

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Interleukin-4
Phosphotyrosine
Insulin Receptor Substrate Proteins
Interleukin-4 Receptors
Myeloid Progenitor Cells
Interleukin-3
Tyrosine
Phosphotransferases
Phosphorylation

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Interleukin 4 signals through two related pathways. / Pernis, Alessandra; Witthuhn, Bruce; Keegan, Achsah D.; Nelms, Keats; Garfein, Evan S.; Ihle, James N.; Paul, William E.; Pierce, Jacalyn H.; Rothman, Paul.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 17, 15.08.1995, p. 7971-7975.

Research output: Contribution to journalArticle

Pernis, A, Witthuhn, B, Keegan, AD, Nelms, K, Garfein, ES, Ihle, JN, Paul, WE, Pierce, JH & Rothman, P 1995, 'Interleukin 4 signals through two related pathways', Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 17, pp. 7971-7975. https://doi.org/10.1073/pnas.92.17.7971
Pernis, Alessandra ; Witthuhn, Bruce ; Keegan, Achsah D. ; Nelms, Keats ; Garfein, Evan S. ; Ihle, James N. ; Paul, William E. ; Pierce, Jacalyn H. ; Rothman, Paul. / Interleukin 4 signals through two related pathways. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 17. pp. 7971-7975.
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