Thyroid cell responses to thyrotropin and 12-O-tetradecanoyl-phorbol-13-acetate: translocation of protein kinase C and phosphorylation of thyroid cell polypeptide substrates.
Thyroid cell responses to thyrotropin and 12-O-tetradecanoyl-phorbol-13-acetate: translocation of protein kinase C and phosphorylation of thyroid cell polypeptide substrates.
复制标题
甲状腺细胞对促甲状腺素和 12-O-十四烷酰基-佛波醇-13-乙酸酯的反应：蛋白激酶 C 的易位和甲状腺细胞多肽底物的磷酸化。
DOI：
10.1016/0003-9861(85)90776-3
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发表时间：
1985
影响因子：
3.9
通讯作者：
Field,JB
中科院分区：
文献类型：
--
作者：
Tanabe,A;Nielsen,TB;Rani,CS;Field,JB
促甲状腺激素（TSH）对甲状腺的作用并非都是由腺苷酸环化酶-环AMP系统的激活介导的，这表明还必须存在其他控制系统。虽然钙磷脂依赖性蛋白激酶（蛋白激酶C）和特定的底物已被确定在甲状腺组织中，他们的反应TSH和其他刺激尚未确定。在甲状腺细胞已预先与[32 P]正磷酸盐，TSH和12-O-十四酰基-佛波醇-13-乙酸酯（TPA）增加磷酸化的33 K多肽底物在5分钟内在剂量依赖性的方式。用1 mU/ml TSH和3 nmTPA观察到效果，用100 mU/ml TSH和100 nmTPA最大。TPA的无生物活性类似物4α-佛波醇没有影响。异丁基甲基黄嘌呤（IBMX）可降低33 K多肽的磷酸化，并抑制TSH和TPA的作用，表明磷酸化不是由cAMP介导的。TSH和IBMX，但不是TPA，增强磷酸化的38 K多肽，表明环AMP的参与。相反，TPA，而不是TSH，增加磷酸化的58 K和28 K多肽。促甲状腺激素（TSH）升高甲状腺片环磷酸腺苷（cAMP）水平，TPA和4α-佛波醇（4α-phorbol）无此作用。用TSH或TPA孵育甲状腺切片，可显著降低100，000 g胞浆组分中的蛋白激酶C活性，并增加质膜提取物中的活性。该效应在5分钟内出现，并在30分钟时达到最大。用100 mU/ml TSH或1 nmTPA观察该效应。TSH或TPA刺激蛋白激酶C并使其从甲状腺组织的胞质溶胶移位到质膜可能提供了控制甲状腺细胞代谢的另一种机制。
Not all of the effects of thyroid-stimulating hormone (TSH) on the thyroid are mediated by activation of the adenylate cyclase-cyclic AMP system, indicating that other control systems must also exist. Although a calcium-phospholipid-dependent protein kinase (protein kinase C) and specific substrates had been identified in thyroid tissue, their responsiveness to TSH and other stimulators has not been determined. In thyroid cells which had been preloaded with [32P]orthophosphate, TSH and 12-O-tetradecanoyl-phor-bol-13-acetate (TPA) increased the phosphorylation of a 33K polypeptide substrate within 5 min in a dose-dependent fashion. The effect was observed with 1 mU/ml TSH and 3 nmTPA and was maximal with 100 mU/ml TSH and 100 nmTPA. The biologically inactive analog of TPA, 4α-phorbol, had no effect. Isobutylmethylxanthine (IBMX) decreased the phosphorylation of the 33K polypeptide and inhibited the effect of TSH and TPA, indicating that the phosphorylation is not mediated by cyclic AMP. TSH and IBMX, but not TPA, augmented phosphorylation of a 38K polypeptide, suggesting involvement of cyclic AMP. In contrast TPA, but not TSH, increased the phosphorylation of 58K and 28K polypeptides. TSH, but not TPA or 4α-phorbol, elevated the cyclic AMP level of thyroid slices. Incubation of thyroid slices with TSH or TPA significantly decreased protein kinase C activity in the 100,000gcytosol fraction and increased it in an extract of plasma membranes. The effect was present within 5 min and was maximal by 30 min. The effect was observed with 100 mU/ml TSH or 1 nmTPA. The stimulation by TSH or TPA of protein kinase C and its translocation from the cytosol to the plasma membranes of thyroid tissue may provide another mechanism for control of thyroid Cell metabolism.