摘要
通过对大鼠肾小球系膜细胞分裂原活化蛋白激酶、ｃ－ｒａｆ－１及ｒａｓ癌基因活性的测定，发现具有酪氨酸蛋白激酶受体的生长因子可以刺激三者快速激活，而蛋白激酶Ｃ活化物佛波醇己酯虽可以激活分裂原活化蛋白激酶，但对ｃ－ｒａｆ－１没有作用。外源性前列腺素Ｅ２（ＰＧＥ２）以及环磷酸腺苷（ｃＡＭＰ）刺激物Ｆｏｒｓｋｏｌｉｎ均可使生长因子刺激引起的分裂原活化蛋白激酶和ｃ－ｒａｆ－１活性受到明显抑制，但对ｒａｓ活性无影响。ＰＭＡ引起的分裂原活化蛋白激酶活性不受ＰＧＥ２的影响。结果提示系膜细胞的分裂原活化蛋白激酶活化至少存在着两条不同的信号传导途径，在病理过程中可能分别介导不同的细胞生长。
ctivation of the mitogenactivated protein kinase(MAPK)
pathway is believed to play a critical role innormal and pathophysiologic prollferation of
mesangialcells. Recent studies have shown that MAP kinase acti-vation by growth factors in
other cell types involves acti-vation of the low molecular weight G-protein ras and
theprotooncogene serine kinase crafl. In this study therole of this pathway in rat renal
mesangial cells was as-sessed. 20ng/ml of platelet-derived growth factor(PDGF) , 10-8 mol/L
epidermal growth factor (EGF)as well as phorbol ester (10-6 mol/L PMA) rapidly acti-vated MAP
kinase bv 3-4 fold in these cells. PDGF andEGF . but not PMA were able to activate c-raf-1 and
rasactivity. Stimulation with inflammatory mediator PGE2(50μmol/L) or elevation of intracellular
cAMP bytreatment of cells with forskolin (25μmol/L) markedlyblunted activation of MAP kinase
induced by PDGF andEGF, but not PMA. Consistent with this observation,PGE2 abolished growth
factor induced activation of c-raf-1. However, ras activation induced by growth factorwas not
affected by PGE2 and forskolin. These resultssuggest that MAP kinase activation can occur by
at leasttwo separate pathways in mesangial cells. Tyrosine ki-nase receptors activate MAP
kinase through activationof ras and raf. This pathway can be blocked by PGE2and elevation of
cAMP, presumably by interfering withthe ability of ras to activate raf. In addition, activationof
protein kinase C by phorbol esters can activate MAPkinase in a ras/raf-independent manner.
This pathwayis not sensitive to inhibition by PGE2 or cAMP. It islikely that activation of each of
these pathways , both re-sulting in a stimulated MAP kinase, will have differentphysiologic
consequences in mediating mesangial cellsgrowth.
出处
《中华医学杂志》
CAS
CSCD
北大核心
1995年第4期207-210,共4页
National Medical Journal of China
基金
美国NIH研究基金
关键词
前列腺素E2
血小板
衍生长因子
Dinoprostone Signal
transductionPlatelet-derived growth factor
