Phospholipase C-γ1 is required for calcium-induced keratinocyte differentiation

被引:65
作者
Xie, ZJ [1 ]
Bikle, DD [1 ]
机构
[1] Univ Calif San Francisco, Vet Affairs Med Ctr, Endocrine Unit, San Francisco, CA 94121 USA
关键词
D O I
10.1074/jbc.274.29.20421
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Phospholipase C-gamma 1 is the most abundant member of the phospholipase C family in keratinocytes and is induced by calcium. Phospholipase C-gamma 1, therefore, may be involved in the signal transduction system leading to calcium regulation of keratinocyte differentiation. To test this hypothesis, expression of phospholipase C-gamma 1 in human keratinocytes was blocked by transfecting cells with the antisense human phospholipase C-gamma 1 cDNA construct. These cells demonstrated a dramatic reduction in phospholipase C-gamma 1 protein level compared with the empty vector-transfected cells and a marked reduction in the mRNA and protein levels of the differentiation markers involucrin and transglutaminase following administration of calcium. Similarly, cotransfection of antisense phospholipase C-gamma 1 constructs with a luciferase reporter vector containing involucrin or transglutaminase promoters led to a substantial reduction in calcium-stimulated involucrin and transglutaminase promoter activities. Similar results were seen following treatment with a specific phospholipase C inhibitor U73122. To determine whether phospholipase C-gamma 1 regulated differentiation by controlling intracellular calcium, we examined the ability of antisense phospholipase C-gamma 1 to block the calcium-induced rise in intracellular calcium and found that it could. These findings indicate that phospholipase C-gamma 1 is a critical component of the signaling pathway mediating calcium regulation of keratinocyte differentiation via its mobilization of intracellular calcium.
引用
收藏
页码:20421 / 20424
页数:4
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