PKC alpha induces differentiation through ERK1/2 phosphorylation in mouse keratinocytes.
- Author:
Haeng Ran SEO
1
;
Yoo Wook KWAN
;
Chul Koo CHO
;
Sangwoo BAE
;
Su Jae LEE
;
Jae Won SOH
;
Hee Yong CHUNG
;
Yun Sil LEE
Author Information
1. Laboratory of Radiation Effect Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong Nowon-Ku, Seoul 139-706, Korea. yslee@kcch.re.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Ca2+-mediated differentiation;
ERK1/2;
mouse keratinocytes;
p38 MAPK;
PKC alpha
- MeSH:
Animals;
Calcium/pharmacology/physiology;
Cell Differentiation/physiology;
Intermediate Filament Proteins/analysis/metabolism;
Keratinocytes/cytology/*enzymology;
Membrane Proteins/analysis/metabolism;
Mice;
Mitogen-Activated Protein Kinase 1/*metabolism;
Mitogen-Activated Protein Kinase 3/*metabolism;
Phosphorylation;
Protein Kinase C/genetics/*physiology;
Research Support, Non-U.S. Gov't;
p38 Mitogen-Activated Protein Kinases/metabolism
- From:Experimental & Molecular Medicine
2004;36(4):292-299
- CountryRepublic of Korea
- Language:English
-
Abstract:
Epidermal keratinocyte differentiation is a tightly regulated stepwise process that requires protein kinase C (PKC) activation. Studies on cultured mouse keraitnocytes induced to differentiate with Ca2+ have indirectly implicated the involvement of PKC alpha isoform. When PKC alpha was overexpressed in undifferentiated keratinocytes using adenoviral system, expressions of differentiation markers such as loricrin, filaggrin, keratin 1 (MK1) and keratin 10 (MK10) were increased, and ERK1/2 phosphorylation was concurrently induced without change of other MAPK such as p38 MAPK and JNK1/2. Similarly, transfection of PKC alphakinase active mutant (PKC alpha- CAT) in the undifferentiated keratinocyte, but not PKC beta-CAT, also increased differentiation marker expressions. On the other hand, PKC alphadominant negative mutant (PKC beta-KR) reduced Ca2+ -mediated differentiation marker expressions, while PKC beta-KR did not, suggesting that PKC alphais responsible for keratinocyte differentiation. When downstream pathway of PKC alphain Ca2+ - mediated differentiation was examined, ERK1/2, p38 MAPK and JNK1/2 phosphorylations were increased by Ca2+ shift. Treatment of keratinocytes with PD98059, MEK inhibitor, and SB20358, p38 MAPK inhibitor, before Ca2+ shift induced morphological changes and reduced expressions of differentiation markers, but treatment with SP60012, JNK1/2 inhibitor, did not change at all. Dominant negative mutants of ERK1/2 and p38 MAPK also inhibited the expressions of differentiation marker expressions in Ca2+ shifted cells. The above results indicate that both ERK1/2 and p38 MAPK may be involved in Ca2+- mediated differentiation, and that only ERK1/2 pathway is specific for PKCa-mediated differentiation in mouse keratinocytes.
