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

2004 ◽  
Vol 164 (7) ◽  
pp. 979-984 ◽  
Author(s):  
Masakiyo Sakaguchi ◽  
Masahiro Miyazaki ◽  
Hiroyuki Sonegawa ◽  
Mariko Kashiwagi ◽  
Motoi Ohba ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Growth Regulation ◽  
Transforming Growth Factor ◽  
Human Keratinocytes ◽  
Transforming Growth Factor Β ◽  
Signal Pathway ◽  
Critical Event ◽  
Kinase C ◽  
Normal Human Keratinocytes ◽  
Normal Human

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 p21WAF1/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.

Modulation of growth and differentiation in normal human keratinocytes by transforming growth factor-β 1

1990 ◽  
Vol 1 (5) ◽  
pp. 394
Author(s):  
Makoto Hashiro ◽  
Hidenobu Okumura ◽  
Kunio Matsumoto ◽  
Koji Hashimoto ◽  
Kunihiko Yoshikawa
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Human Keratinocytes ◽  
Transforming Growth Factor Β ◽  
Normal Human Keratinocytes ◽  
Normal Human

scholarly journals Absence of Down-Regulation and Translocation of The η Isoform of Protein Kinase C in Normal Human Keratinocytes

1996 ◽  
Vol 106 (4) ◽  
pp. 790-794 ◽  
Author(s):  
Akiko Murakami ◽  
Kazuhiro Chida ◽  
Yasutoshi Suzuki ◽  
Hidehiko Kikuchi ◽  
Shinobu Imajoh-Ohmi ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Human Keratinocytes ◽  
Down Regulation ◽  
Kinase C ◽  
Normal Human Keratinocytes ◽  
Normal Human

scholarly journals S100A11, an Dual Mediator for Growth Regulation of Human Keratinocytes

2008 ◽  
Vol 19 (1) ◽  
pp. 78-85 ◽  
Author(s):  
Masakiyo Sakaguchi ◽  
Hiroyuki Sonegawa ◽  
Hitoshi Murata ◽  
Midori Kitazoe ◽  
Jun-ichiro Futami ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Regulation ◽  
Transforming Growth Factor ◽  
Human Keratinocytes ◽  
Transforming Growth Factor Β ◽  
Growth Stimulation ◽  
Nuclear Factor Κb ◽  
Camp Response Element Binding ◽  
Element Binding Protein ◽  
Squamous Cancer

We previously revealed a novel signal pathway involving S100A11 for inhibition of the growth of normal human keratinocytes (NHK) caused by high Ca++ or transforming growth factor β. Exposure to either agent resulted in transfer of S100A11 to nuclei, where it induced p21WAF1. In contrast, S100A11 has been shown to be overexpressed in many human cancers. To address this apparent discrepancy, we analyzed possible new functions of S100A11, and we provide herein evidence that 1) S100A11 is actively secreted by NHK; 2) extracellular S100A11 acts on NHK to enhance the production of epidermal growth factor family proteins, resulting in growth stimulation; 3) receptor for advanced glycation end products, nuclear factor-κB, Akt, and cAMP response element-binding protein are involved in the S100A11-triggered signal transduction; and 4) production and secretion of S100A11 are markedly enhanced in human squamous cancer cells. These findings indicate that S100A11 plays a dual role in growth regulation of epithelial cells.

scholarly journals Induction of Differentiation in Normal Human Keratinocytes by Adenovirus-Mediated Introduction of the η and δ Isoforms of Protein Kinase C

1998 ◽  
Vol 18 (9) ◽  
pp. 5199-5207 ◽  
Author(s):  
Motoi Ohba ◽  
Keiko Ishino ◽  
Mariko Kashiwagi ◽  
Shoko Kawabe ◽  
Kazuhiro Chida ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Cell Differentiation ◽  
Protein Kinase ◽  
Squamous Cell ◽  
Human Keratinocytes ◽  
Kinase C ◽  
Normal Human Keratinocytes ◽  
Transglutaminase 1 ◽  
Normal Human ◽  
Human And Mouse

ABSTRACT Protein kinase C (PKC) plays a crucial role(s) in regulation of growth and differentiation of cells. In the present study, we examined possible roles of the α, δ, η, and ζ isoforms of PKC in squamous differentiation by overexpressing these genes in normal human keratinocytes. Because of the difficulty of introducing foreign genes into keratinocytes, we used an adenovirus vector system, Ax, which allows expression of these genes at a high level in almost all the cells infected for at least 72 h. Increased kinase activity was demonstrated in the cells overexpressing the α, δ, and η isoforms. Overexpression of the η isoform inhibited the growth of keratinocytes of humans and mice in a dose (multiplicity of infection [MOI])-dependent manner, leading to G1 arrest. The η-overexpressing cells became enlarged and flattened, showing squamous cell phenotypes. Expression and activity of transglutaminase 1, a key enzyme of squamous cell differentiation, were induced in the η-overexpressing cells in dose (MOI)- and time-dependent manners. The inhibition of growth and the induction of transglutaminase 1 activity were found only in the cells that express the η isoform endogenously, i.e., in human and mouse keratinocytes but not in human and mouse fibroblasts or COS1 cells. A dominant-negative η isoform counteracted the induction of transglutaminase 1 by differentiation inducers such as a phorbol ester, 1α,25-dihydroxyvitamin D3, and a high concentration of Ca2+. Among the isoforms examined, the δ isoform also inhibited the growth of keratinocytes and induced transglutaminase 1, but the α and ζ isoforms did not. These findings indicate that the η and δ isoforms of PKC are involved crucially in squamous cell differentiation.

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