Interleukin-1-inducible expression of gro-β via NF-κB activation is dependent upon tyrosine kinase signaling

S. S. Joshi-Barve, V. V. Rangnekar, S. F. Sells, V. M. Rangnekar

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Interleukin-1 (IL-1) induces programmed growth arrest in human melanoma cells, A375-C6. IL-1 action in these cells is associated with induction of a cell type-specific immediate-early (IE) gene expression program characterized by strong, rapid, and sustained induction of gro-α and gro-β, but transient induction of c-jun, IRG-9, and NAK-1, and lack of induction of c-myc. With the exception of gro-α and gro-β, these IE genes are also associated with growth-stimulatory responses in the melanoma cells, suggesting that the gro- genes may play key roles in the growth arrest action of the cytokine. To elucidate the early intracellular signals associated with IL-1 action, we are studying the second messenger signals and transcription factors required for induction of gro-genes. Here, we present evidence that IL-1-inducible gro- gene expression is dependent on tyrosine kinase signaling. Using gel retardation and transient expression assays, we show that IL-1 causes protein tyrosine phosphorylation-dependent activation of NF-κB enhancer binding protein, which then induces transcription of the gro-genes via an NF-κB site located 76 base pairs upstream from the cap site. IL-1-activated protein tyrosine phosphorylation is also required for gro-gene induction in human cervical carcinoma cells, HeLa; human fibroblast cells, WI-38; and mouse fibroblast cells, L929. Thus, in diverse cell types, IL-1 induces gro-genes via tyrosine kinase-dependent signals.

Original languageEnglish
Pages (from-to)18018-18029
Number of pages12
JournalJournal of Biological Chemistry
Issue number24
StatePublished - 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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