RRC ID 67967
Author Funaba M, Murakami M, Ikeda T, Ogawa K, Tsuchida K, Sugino H.
Title Identification of tocopherol-associated protein as an activin/TGF-beta-inducible gene in mast cells.
Journal Biochim Biophys Acta
Abstract Previous studies have demonstrated that treatment with activin A and TGF-beta(1), members of the TGF-beta family, stimulated maturation of mouse bone marrow-derived cultured mast cells (BMMC), which was characterized by morphology and gene expression of mouse mast cell proteases (mmcps). In order to gain a better understanding of activin A- and TGF-beta(1)-induced maturation in mast cells, we investigated the genes that were up-regulated in response to treatment with these two members of the TGF-beta family. The cDNA microarray analyses indicated that in BMMC, five genes were induced by treatment with 4 nM activin A for 2 h. Tocopherol-associated protein (Tap) was one of the induced genes, and the Tap induction in response to activin A treatment was confirmed by real-time RT-PCR analyses. Treatment with TGF-beta(1) at 200 pM but not BMP-2 at 4 nM also increased Tap gene transcript in BMMC. Activin A-induced Tap expression was detected in BMMC but not in RAW264 macrophage-like cells, B16 melanoma cells or P19 embryonic carcinoma cells. Treatment with >1 muM SB431542, an inhibitor of activin and TGF-beta type I receptors ALK4/5, reduced responsiveness of Tap expression to TGF-beta(1), whereas <0.5 microM SB431542 effectively reduced TGF-beta(1)-induced expression of mmcp-1 and mmcp-7. These results suggest that inhibitory effects of SB431542 are different between TGF-beta-induced genes. Reporter assays indicated that Tap expression enhances transcription mediated by the activin/TGF-beta pathway. Thus, the present results suggest that Tap induction in response to activin/TGF-beta occurs predominantly in mast cells and serves as a positive regulator in activin/TGF-beta signaling.
Volume 1763(8)
Pages 900-6
Published 2006-8-1
DOI 10.1016/j.bbamcr.2006.06.002
PII S0167-4889(06)00118-2
PMID 16872693
MeSH Activin Receptors, Type I / antagonists & inhibitors Activins / antagonists & inhibitors Activins / pharmacology* Animals Benzamides / pharmacology Carrier Proteins / genetics* Cell Line Cells, Cultured DNA, Complementary / genetics Dioxoles / pharmacology Gene Expression Regulation / drug effects Inhibin-beta Subunits / antagonists & inhibitors Inhibin-beta Subunits / pharmacology* Lipoproteins / genetics* MAP Kinase Signaling System Mast Cells / drug effects* Mast Cells / metabolism* Mice Oligonucleotide Array Sequence Analysis Receptors, Transforming Growth Factor beta / antagonists & inhibitors Signal Transduction Smad3 Protein / deficiency Smad3 Protein / genetics Trans-Activators / genetics* Transforming Growth Factor beta / antagonists & inhibitors Transforming Growth Factor beta / pharmacology* Transforming Growth Factor beta1
IF 3.411
Human and Animal Cells RAW 264(RCB0535) Hep G2