Abstract
Interactions between various signaling pathways enable a fine control of cellular activities. When the cells are subjected to activation of TGF-β signaling and PKC signaling, PKC phosphorylation of Smad3 abrogates binding and transcriptional activity of Smad3 leading to suppression of TGF-β response [1]. We studied this interaction between Smads and PKC in different cell types to examine cell specificity of the interaction. We found that the outcome of the interaction between Smads and PKC depends on cell types and inducibility of a regulatory molecule Tsc-22. In this report, we showed that induced Tsc-22 leads to enhancement of TGF-β-dependent signaling and the enhancement was blocked by expression of a dominant-negative Tsc-22 mutant. Its effect on cellular differentiation was also examined.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- TGF-β:
-
Transforming growth factor-β
- PKC:
-
Protein kinase C
- PMA:
-
Phorbol 12-myristate 13-acetate
References
Yakymvych I, Ten Dijke P, Heldin CH, Souchelnytskyi S (2001) Regulation of Smad signaling by protein kinase C. FASEB J 15:553–555
Massague J, Wotton D (2000) Transcriptional control by the TGF-β/Smad signaling system. EMBO J 19:1745–1754
Itoh S, Itoh F, Goumans M, Ten Dijke P (2000) Signaling of transforming growth factor-β family members through Smad proteins. Eur J Biochem 267:6954–6967
Shibanuma M, Kuroki T, Nose K (1992) Isolation of a gene encoding a putative leucine zipper structure that is induced by transforming growth factor beta 1 and other growth factors. J Biol Chem 267:10219–10224
Kester HA, Blanchetot C, den Hertog J, van der Saag PT, van der Burg B (1999) Transforming growth facor-beta-stimulated clone-22 is a member of a family of leucine-zipper proteins that can homodimerize and heterodimerize and has transcriptional repressor activity. J Biol Chem 274:27439–27447
Hino S, Kawamata H, Uchida D, Omotehara F, Miwa Y, Begum NM, Yoshida H, Fujimori T, Sato M (2000) Nuclear translocation of Tsc-22 concomitant with apoptosis: Tsc-22 as a putative transcriptional regulator. Biochem Biophys Res Commun 278:659–664
Choi S, Moon J, Ahn Y, Ahn J, Kim D, Han T (2005) Tsc-22 enhances TGF-β signaling by associating with Smad4 and induces erythroid cell differentiation. Mol Cell Biochem 271:23–28
Gupta RA, Sarra P, Brockman JA, Shappell SB, Raftery LA, Wilson TM, Dubois RN (2003) Peroxisome proliferator-acrivated receptor г and transforming growth factor-β pathways inhibit intestinal epithelial cell growth by regulating levels of Tsc-22. J Biol Chem 9:7431–7438
Wotton D, Lo RS, Lee S, Massague J (1999) A Smad transcriptional corepressor. Cell 97:29–39
Shin HM, Seoh JY, Chung HY, Choi SJ, Hahn MJ, Kang JS, Choi MS, Han TH (1999) Requirement of MEF2D in the induced differentiation of HL60 promyeloid cells. Mol Immunol 36:1209–1214
Taketani S, Furukawa T, Furuyama K (2001) Expression of coproporphyrinogen oxidase and synthesis of hemoglobin in human erythroleukemia K562 cell. Eur J Biochem 268:1705–1711
Uchida D, Omotechara F, Nakashiro K, Tateishi Y, Hino S, Begum NM, Fujimori T, Kawamata H (2003) Posttranscriptional regulation of Tsc-22 (TGF-β-stimulated clone-22) gene by TGF-β1. Biochem Biophys Res Commun 305:846–854
Lu Y, Kitaura J, Oki T, Komeno Y, Ozaki K, Kiyono M, Kumagai H, Nakajima H, Nosaka T, Aburatani H, Kitamura T (2007) Identification of Tsc-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD. Leukemia 11:2246–2257
Acknowledgments
We thank Dr. Joan Massague for plasmid. This study was supported by Samsung Biomedical Research Institute Grant.