HORMONAL-REGULATION OF MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVITY IN BOVINE ADRENOCORTICAL-CELLS - CROSS-TALK BETWEEN PHOSPHOINOSITIDES, ADENOSINE-3',5'-MONOPHOSPHATE, AND TYROSINE KINASE RECEPTOR PATHWAYS
HORMONAL-REGULATION OF MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVITY IN BOVINE ADRENOCORTICAL-CELLS - CROSS-TALK BETWEEN PHOSPHOINOSITIDES, ADENOSINE-3',5'-MONOPHOSPHATE, AND TYROSINE KINASE RECEPTOR PATHWAYS
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DOI：
10.1210/en.136.3.956
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发表时间：
1995-03-01
期刊：
影响因子：
4.8
通讯作者：
VILGRAIN, I
中科院分区：
文献类型：
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作者：
CHABRE, O;CORNILLON, F;VILGRAIN, I
血管紧张素II（AII）通过磷酸肌醇途径刺激牛肾上腺皮质（BAC）细胞中的类固醇生成，在处理5分钟后激活p42-p44促分裂原活化蛋白激酶（MAPK）（EC（50）= 0.1 nM）。这种激活作用1）可被AII受体AT（1）亚型拮抗剂Dup 753（10 μ M）I完全抑制，但不受AT（2）拮抗剂PD 123177的影响; 2）不能被AT（2）激动剂CGP 42112 A复制; 3）对百日咳毒素预处理不敏感;和4）通过将细胞预暴露于佛波酯12-O-十四酰基佛波酯13-乙酸酯48小时而消除（TPA; 1 μ M），其下调蛋白激酶-C活性。成纤维细胞生长因子-2，一种对BAC细胞有效的有丝分裂原，通过其酪氨酸激酶受体起作用的ACTH也以TPA不敏感的方式激活MAPK（EC（50）= 0.3ng/ml），而对BAC细胞类固醇生成没有可检测的作用。事实上，ACTH完全阻断（IC 50 = 0.01 nM）AII、成纤维细胞生长因子-2或TPA对MAPK的刺激。因此，牛肾上腺皮质细胞通过肌醇、cAMP和生长因子激活的酪氨酸激酶途径之间的相互作用提供了MAPK活性的正性和负性激素调节的实例。
Angiotensin-II (AII), which stimulates steroidogenesis in bovine adrenocortical (BAC) cells through the phosphoinositides pathway, activates p42-p44 mitogen-activated protein kinases (MAPKs) after 5 min of treatment (EC(50) = 0.1 nM). This activation is 1) completely inhibited by the AII receptor AT(1) subtype antagonist Dup 753 (10 mu M)I but unaffected by the AT(2) antagonist PD 123177; 2) not reproduced by the AT(2) agonist CGP 42112A; 3) insensitive to pretreatment with pertussis toxin; and 4) abolished by a 48-h preexposure of the cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA; 1 mu M), which down-regulates protein kinase-C activity.Fibroblast growth factor-2, a potent mitogen far BAC cells, which acts through its tyrosine kinase receptor, also activates MAPK (EC(50) = 0.3 ng/ml) in a TPA-insensitive manner, while exhibiting no detectable effect on BAC cell steroidogenesis.In contrast, ACTH, which stimulates steroidogenesis via cAMP and inhibits BAC cell proliferation, does not stimulate MAPK. Indeed, ACTH completely blocks (IC50 = 0.01 nM) the stimulation of MAPK by AII, fibroblast growth factor-2, or TPA.Therefore, bovine adrenocortical cells provide an example of positive and negative hormonal regulation of MAPK activity through a cross-talk between the inositide-, cAMP-, and growth factor-activated tyrosine kinase pathways.