EVIDENCE FOR INVOLVEMENT OF PHOSPHATIDYLCHOLINE-PHOSPHOLIPASE-C AND PROTEIN-KINASE-C IN TRANSFORMING GROWTH-FACTOR-BETA SIGNALING

被引：90

作者：

HALSTEAD, J ^{[1
]}

KEMP, A ^{[1
]}

IGNOTZ, RA ^{[1
]}

机构：

[1] UNIV MASSACHUSETTS,MED CTR,DEPT CELL BIOL,WORCESTER,MA 01655

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 1995年 / 270卷 / 23期

关键词：

D O I：

10.1074/jbc.270.23.13600

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：

Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that elicits a wide variety of responses in cells. TGF-beta binds to cell surface receptors that contain cytoplasmic serine/threonine kinase domains. Here we provide evidence that both phospholipase C and protein kinase C (pFC) are involved in the TGF-beta activation of transcription and luciferase expression from the p3TP-Lux plasmid. Down-regulation of PKC prevents TGF-beta 1 induction of luciferase expression. Staurosporin and Calphostin C, inhibitors of PKC, block the ability of TGF-beta 1 to initiate transcription of the luciferase gene. Further, D609, an inhibitor of phosphatidylcholine-phospholipase C (PC-PLC), and secondarily PKC also blocks TGF-1-induced transcription of the transgene in A549 cells while the phosphatidylinositol-PLC pathway inhibitor U73122 is without effect; TGF-beta elevates steady-state mRNA levels for the endogenous PAI-1 and fibronectin genes. Treatment of cells with calphostin C or D609 prevents the TGF-beta-induced increase in these mRNAs. Together, these results suggest that PC-PLC and PKC are in a TGF-beta signaling pathway that results in elevated gene expression.

引用

页码：13600 / 13603

页数：4

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