Ausiello D A, Rosenblatt M, Dayer J M
Am J Physiol. 1980 Aug;239(2):E144-9. doi: 10.1152/ajpendo.1980.239.2.E144.
The physiological effects of parathyroid hormone (PTH) in bone are mediated at least in part by cyclic AMP. The biochemical events subsequent to this step have not been well characterized in this tissue. Giant cell tumors of bone (GT) increase cyclic AMP in response to PTH. This response can be inhibited by an analogue of bovine PTH, [Nle8, Nle18, Tyr34] bPTH-(3-34) amide (PTH-Inh). Cyclic AMP content and cyclic AMP-dependent protein kinase (cAMP-PK) were assayed in fresh tumors and cells in culture incubated with 1 microgram/ml of bPTH and/or PTH-Inh. PTH fully activated cAMP-PK in GT, and PTH-Inh completely inhibited PTH-stimulated increases in cyclic AMP content and cAMP-PK activity. When endogenous protein substrates were sought for cAMP-PK, three phosphoproteins of 55,000, 43,000, and 38,000 mol wt maximally increased their phosphorylation by 30% after 12-min incubation with bPTH. Dephosphorylation of proteins of 200,000 and 120,000 mol wt was also observed. These data are consistent with the hypothesis that PTH action in bone is mediated by the phosphorylation and dephosphorylation of specific substrates.
甲状旁腺激素（PTH）对骨骼的生理作用至少部分是由环磷酸腺苷（cAMP）介导的。在该组织中，这一步骤之后的生化事件尚未得到充分表征。骨巨细胞瘤（GT）对PTH有反应，会增加环磷酸腺苷。这种反应可被牛PTH的类似物[Nle8，Nle18，Tyr34]bPTH-(3-34)酰胺（PTH-Inh）抑制。用1微克/毫升的bPTH和/或PTH-Inh孵育新鲜肿瘤和培养细胞后，测定环磷酸腺苷含量和环磷酸腺苷依赖性蛋白激酶（cAMP-PK）。PTH在GT中完全激活了cAMP-PK，而PTH-Inh完全抑制了PTH刺激的环磷酸腺苷含量和cAMP-PK活性的增加。当寻找cAMP-PK的内源性蛋白质底物时，与bPTH孵育12分钟后，三种分子量分别为55,000、43,000和38,000的磷蛋白最大程度地增加了30%的磷酸化。还观察到分子量为200,000和120,000的蛋白质的去磷酸化。这些数据与PTH在骨骼中的作用是由特定底物的磷酸化和去磷酸化介导的这一假设一致。
