Calcium prevents retinoic acid-induced disruption of the spectrin-based cytoskeleton in keratinocytes through the Src/PI3K-p85 alpha/AKT/PKC delta/beta-adducin pathways

Zhao, Kong-Nan, Masci, Paul P., Chen, Jiezhong and Lavin, Martin F. (2013) Calcium prevents retinoic acid-induced disruption of the spectrin-based cytoskeleton in keratinocytes through the Src/PI3K-p85 alpha/AKT/PKC delta/beta-adducin pathways. Cell Calcium, 54 3: 151-162. doi:10.1016/j.ceca.2013.05.009


Author Zhao, Kong-Nan
Masci, Paul P.
Chen, Jiezhong
Lavin, Martin F.
Title Calcium prevents retinoic acid-induced disruption of the spectrin-based cytoskeleton in keratinocytes through the Src/PI3K-p85 alpha/AKT/PKC delta/beta-adducin pathways
Journal name Cell Calcium   Check publisher's open access policy
ISSN 0143-4160
1532-1991
Publication date 2013-09-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.ceca.2013.05.009
Open Access Status Not Open Access
Volume 54
Issue 3
Start page 151
End page 162
Total pages 12
Place of publication London, United Kingdom
Publisher Churchill Livingstone
Language eng
Formatted abstract
We have previously reported that spectrin increases dramatically in amount and is assembled into the cytoskeleton in differentiating keratinocytes both in vitro and in vivo (Zhao et al., PLoS ONE 6 (12) (2011) e28267). We demonstrate here that extracellular calcium (Ca2+) enhances differentiation of keratinocytes and that this is associated with increased spectrin expression and formation of a spectrin-based cytoskeleton. While Retinoic acid (RA) also enhanced keratinocyte differentiation, it abrogated the spectrin-based cytoskeleton in keratinocytes. Furthermore, RA substantially inhibited expression of both Src and PI3K-p85α and consequently the amounts of specific phosphorylation of both of these proteins. RA also enhanced AKT expression and dramatically induced phosphorylation of AKT(Thr308), accompanied by phosphorylation of both PKCδ(Thr505) and β-adducin(Ser662) and upregulated cyclin D2 and down-regulated cyclin B1. On the other hand, Ca2+ overcame the inhibitory effects of RA on expression of Src, PI3K-p85α and cyclin B1 by maintaining high levels of phosphorylation of both Src(Tyr527) and PI3K-p85α and preventing phosphorylation of AKT(Thr308), PKCδ(Thr505) and β-adducin(Ser662). These data highlight the importance of Ca2+ in both spectrin expression and the organizational integrity of the spectrin-based cytoskeleton in differentiating keratinocytes and assist in elucidating the signalling pathways involved.
Keyword Calcium
Retinoic acid
Spectrin-based cytoskeleton
Cell differentiation
Keratinocyte differentiation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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