PKCα mediates TGFβ-induced growth inhibition of human keratinocytes via phosphorylation of S100C/A11

Masakiyo Sakaguchi, Masahiro Miyazaki, Hiroyuki Sonegawa, Mariko Kashiwagi, Motoi Ohba, Toshio Kuroki, Masayoshi Namba, Nam Ho Huh

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67 Citations (Scopus)

Abstract

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. 163:825-835). This paper addresses a question whether transforming growth factor β (TGFβ) shares the pathway with high Ca2+. On exposure of the cells to TGFβ1, S100C/A11 was phosphorylated, bound to nucleolin, and transferred to the nucleus, resulting in induction of p21 WAF1/CIP1 and p15INK4B through activation of Sp1. Protein kinase C α (PKCα) was shown to phosphorylate 10Thr of S100C/A11, which is a critical event for the signal transduction. The TGFβ1-induced growth inhibition was almost completely mitigated when PKCα activity was blocked or when S100C/A11 was functionally sequestered. These results indicate that, in addition to the well-characterized Smad-mediated pathway, the PKCα-S100C/A11-mediated pathway is involved in and essential for the growth inhibition of normal human keratinocytes cells by TGFβ1.

Original languageEnglish
Pages (from-to)979-984
Number of pages6
JournalJournal of Cell Biology
Volume164
Issue number7
DOIs
Publication statusPublished - Mar 29 2004

Keywords

  • Calcium
  • Nucleolin
  • PKC
  • S100
  • p21

ASJC Scopus subject areas

  • Cell Biology

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