Intracellular signaling of gp34, the OX40 ligand: induction of c-jun and c-fos mRNA expression through gp34 upon binding of its receptor, OX40.
We investigated the intracellular signaling events of OX40 ligand (gp34), a member of the TNF family. To elucidate the intracellular signaling via gp34, we prepared a model system in which a human gp34-transfected mouse epithelial cell line was stimulated with a recombinant soluble form of OX40. We demonstrated that OX40 binding resulted in increase in c-jun and c-fos mRNA levels in this transfectant by Northern blot analysis, which was blocked by the pretreatment with anti-gp34 Ab. The studies with various gp34 deletion mutants showed that the cytoplasmic portion including the amino acid sequence 16-21 (RPRFER) was required for the induction of c-jun and c-fos mRNA expression. Furthermore, OX40 binding induced c-jun mRNA expression also in HUVECs, which in our previous study have been shown to express gp34 and interact with activated T cells through the OX40/gp34 pathway. On the other hand, c-fos mRNA was detectable neither in unstimulated HUVECs nor in gp34-stimulated HUVECs. These results indicate that the OX40/gp34 system generates two-way signals and may elicit biological effects on vascular endothelial cells.
Matsumura
Y
Y
Department of Hematology and Oncology, Research Center for Acquired Immunodeficiency Syndrome, The Institute for Virus Research, Kyoto University, Japan.
Hori
T
T
Kawamata
S
S
Imura
A
A
Uchiyama
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface; D019556:COS Cells; D002460:Cell Line; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051379:Mice; D053278:OX40 Ligand; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011971:Receptors, Immunologic / Q000378:metabolism*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology*; D012995:Solubility; D014158:Transcription, Genetic / Q000276:immunology; D014162:Transfection; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*; D048069:Tumor Necrosis Factors
D000954:Antigens, Surface; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053278:OX40 Ligand; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C505716:TNFRSF4 protein, human; C089251:TNFSF4 protein, human; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors