Pemphigus IgG activates and translocates protein kinase C from the cytosol to the particulate/cytoskeleton fractions in human keratinocytes

被引:99
作者
Osada, K [1 ]
Seishima, M [1 ]
Kitajima, Y [1 ]
机构
[1] GIFU UNIV,SCH MED,DEPT DERMATOL,GIFU 500,JAPAN
关键词
bullous disease; signal transduction;
D O I
10.1111/1523-1747.ep12289726
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
We have demonstrated previously that pemphigus vulgaris (PV)-IgG induces activation of phospholipase C (PLC), production of inositol 1,4,5-trisphosphate, and a rapid transient increase in [Ca2+](i) in cultured human keratinocytes, leading to secretion of plasminogen activator and cell- cell detachment in cell culture. In the current study, to examine the involvement of protein kinase C (PKC) in the mechanism of blister formation in PV, we studied the PV-IgG-induced translocation of PKC isozymes from the cytosol to the particulate/cytoskeleton (p/c) fractions and the activation of PKC in human keratinocytes. Cells cultured in Eagle's minimum essential medium were incubated with PV-IgGs for 30 s, 1 min, 5 min, or 30 min, PV-IgG binding to the cell surface antigen (desmoglein III) induced translocation of PKC-alpha from the cytosol to the p/c fractions within 30 s, with a peak at 1 min that lasted at least 30 min. PKC-S also was translocated within 1 min and reached a peak at 5 min but was reduced to basal levels at 30 min, Alternatively, PKC-eta translocation to the p/c fraction was induced slowly, taking more than 5 min, and was reduced to approximately half-maximum at 30 min, whereas PKC-zeta translocation reached a maximum at 30 s, rapidly returning to baseline by 5 min after PV-IgG stimulation. The total PKC activity in the p/c fraction also was increased after PV-IgG exposure, peaked at 1. min, and was sustained for at least 30 min. These findings suggest that a unique activation profile of PKC isomers may be involved in mediating the intracellular signaling events induced by PV-IgG binding to desmoglein III in cultured human keratinocytes.
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页码:482 / 487
页数:6
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