Interleukin-1-inducible expression of gro-beta via NF-kappa B activation is dependent upon tyrosine kinase signaling.
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-alpha and gro-beta, but transient induction of c-jun, IRG-9, and NAK-1, and lack of induction of c-myc. With the exception of gro-alpha and gro-beta, 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-kappa B enhancer binding protein, which then induces transcription of the gro-genes via an NF-kappa B 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.
Joshi-Barve
S S
SS
Department of Surgery, University of Kentucky, Lexington 40536.
Rangnekar
V V
VV
Sells
S F
SF
Rangnekar
V M
VM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000235:genetics; D005576:Colforsin / Q000494:pharmacology; D003587:Cytomegalovirus / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016758:Genes, jun; D016259:Genes, myc; D019833:Genistein; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D007739:L Cells; D008545:Melanoma; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D007529:Isoflavones; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; D005576:Colforsin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine