Published 29 March 2004. doi:10.1083/jcb.200312041
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 7, 979-984
PKC
mediates TGFß-induced growth inhibition of human keratinocytes via phosphorylation of S100C/A11
Masakiyo Sakaguchi1,
Masahiro Miyazaki1,
Hiroyuki Sonegawa1,
Mariko Kashiwagi2,
Motoi Ohba2,
Toshio Kuroki3,
Masayoshi Namba4, and
Nam-ho Huh1
1 Department of Cell Biology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan
2 Institute of Molecular Oncology, Showa University, Tokyo 142-8555, Japan
3 Gifu University, Gifu 501-1193, Japan
4 Niimi College, Niimi 718-8585, Japan
Address correspondence to Nam-ho Huh, Dept. of Cell Biology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikatachou, Okayama 700-8558, Japan. Tel.: 81-86-235-7393. Fax: 81-86-235-7400. email: namu{at}md.okayama-u.ac.jp
Growth regulation of epithelial cells is of major concern because most human cancers arise from them. We demonstrated previously a novel signal pathway involving S100C/A11 for high Ca2+-induced growth inhibition of normal human keratinocytes (Sakaguchi, M., M. Miyazaki, M. Takaishi, Y. Sakaguchi, E. Makino, N. Kataoka, H. Yamada, M. Namba, and N.H. Huh. 2003. J. Cell Biol. 163:825835). This paper addresses a question whether transforming growth factor ß (TGFß) shares the pathway with high Ca2+. On exposure of the cells to TGFß1, S100C/A11 was phosphorylated, bound to nucleolin, and transferred to the nucleus, resulting in induction of p21WAF1/CIP1 and p15INK4B through activation of Sp1. Protein kinase C
(PKC
) was shown to phosphorylate 10Thr of S100C/A11, which is a critical event for the signal transduction. The TGFß1-induced growth inhibition was almost completely mitigated when PKC
activity was blocked or when S100C/A11 was functionally sequestered. These results indicate that, in addition to the well-characterized Smad-mediated pathway, the PKC
S100C/A11-mediated pathway is involved in and essential for the growth inhibition of normal human keratinocytes cells by TGFß1.
Key Words: calcium; nucleolin; p21WAF1/CIP1; PKC; S100
The online version of this article contains supplemental material.
Abbreviations used in this paper: NHK, normal human keratinocyte; PEI, polyethylenimine; TGFß, transforming growth factor ß.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
Related Article
-
Two arms of TGFß signaling
- Nicole LeBrasseur
J. Cell Biol. 2004 164: 951.
[Full Text]
[PDF]
This article has been cited by other articles:
-
Murzik, U., Hemmerich, P., Weidtkamp-Peters, S., Ulbricht, T., Bussen, W., Hentschel, J., von Eggeling, F., Melle, C.
(2008). Rad54B Targeting to DNA Double-Strand Break Repair Sites Requires Complex Formation with S100A11. Mol. Biol. Cell
19: 2926-2935
[Abstract]
[Full Text]
-
Chow, J. Y. C., Dong, H., Quach, K. T., Van Nguyen, P. N., Chen, K., Carethers, J. M.
(2008). TGF-{beta} mediates PTEN suppression and cell motility through calcium-dependent PKC-{alpha} activation in pancreatic cancer cells. Am. J. Physiol. Gastrointest. Liver Physiol.
294: G899-G905
[Abstract]
[Full Text]
-
Meran, S., Thomas, D. W., Stephens, P., Enoch, S., Martin, J., Steadman, R., Phillips, A. O.
(2008). Hyaluronan Facilitates Transforming Growth Factor-{beta}1-mediated Fibroblast Proliferation. J. Biol. Chem.
283: 6530-6545
[Abstract]
[Full Text]
-
Sakaguchi, M., Sonegawa, H., Murata, H., Kitazoe, M., Futami, J.-i., Kataoka, K., Yamada, H., Huh, N.-h.
(2008). S100A11, an Dual Mediator for Growth Regulation of Human Keratinocytes. Mol. Biol. Cell
19: 78-85
[Abstract]
[Full Text]
-
Berg, D. T., Gupta, A., Richardson, M. A., O'Brien, L. A., Calnek, D., Grinnell, B. W.
(2007). Negative Regulation of Inducible Nitric-oxide Synthase Expression Mediated through Transforming Growth Factor- -dependent Modulation of Transcription Factor TCF11. J. Biol. Chem.
282: 36837-36844
[Abstract]
[Full Text]
-
Zhu, W., Xu, P., Cuascut, F. X., Hall, A. K., Oxford, G. S.
(2007). Activin Acutely Sensitizes Dorsal Root Ganglion Neurons and Induces Hyperalgesia via PKC-Mediated Potentiation of Transient Receptor Potential Vanilloid I. J. Neurosci.
27: 13770-13780
[Abstract]
[Full Text]
-
Sakaguchi, M., Murata, H., Sonegawa, H., Sakaguchi, Y., Futami, J.-i., Kitazoe, M., Yamada, H., Huh, N.-h.
(2007). Truncation of Annexin A1 Is a Regulatory Lever for Linking Epidermal Growth Factor Signaling with Cytosolic Phospholipase A2 in Normal and Malignant Squamous Epithelial Cells. J. Biol. Chem.
282: 35679-35686
[Abstract]
[Full Text]
-
Hwang, J., Kalinin, A., Hwang, M., Anderson, D. E., Kim, M. J., Stojadinovic, O., Tomic-Canic, M., Lee, S. H., Morasso, M. I.
(2007). Role of Scarf and Its Binding Target Proteins in Epidermal Calcium Homeostasis. J. Biol. Chem.
282: 18645-18653
[Abstract]
[Full Text]
-
Hizli, A. A., Black, A. R., Pysz, M. A., Black, J. D.
(2006). Protein Kinase C {alpha} Signaling Inhibits Cyclin D1 Translation in Intestinal Epithelial Cells. J. Biol. Chem.
281: 14596-14603
[Abstract]
[Full Text]
-
Pfeifhofer, C., Gruber, T., Letschka, T., Thuille, N., Lutz-Nicoladoni, C., Hermann-Kleiter, N., Braun, U., Leitges, M., Baier, G.
(2006). Defective IgG2a/2b Class Switching in PKC{alpha}-/- Mice. J. Immunol.
176: 6004-6011
[Abstract]
[Full Text]
-
Cecil, D. L., Johnson, K., Rediske, J., Lotz, M., Schmidt, A. M., Terkeltaub, R.
(2005). Inflammation-Induced Chondrocyte Hypertrophy Is Driven by Receptor for Advanced Glycation End Products. J. Immunol.
175: 8296-8302
[Abstract]
[Full Text]
-
Sakaguchi, M., Sonegawa, H., Nukui, T., Sakaguchi, Y., Miyazaki, M., Namba, M., Huh, N.-h.
(2005). Bifurcated converging pathways for high Ca2+- and TGF{beta}-induced inhibition of growth of normal human keratinocytes. Proc. Natl. Acad. Sci. USA
102: 13921-13926
[Abstract]
[Full Text]
-
Hara, T., Saito, Y., Hirai, T., Nakamura, K., Nakao, K., Katsuki, M., Chida, K.
(2005). Deficiency of Protein Kinase C{alpha} in Mice Results in Impairment of Epidermal Hyperplasia and Enhancement of Tumor Formation in Two-Stage Skin Carcinogenesis. Cancer Res.
65: 7356-7362
[Abstract]
[Full Text]
-
Moustakas, A., Heldin, C.-H.
(2005). Non-Smad TGF-{beta} signals. J. Cell Sci.
118: 3573-3584
[Abstract]
[Full Text]