Differential effects of cyclic adenosine 3′,5′-monophosphate on p70 ribosomal S6 kinase
Differential effects of cyclic adenosine 3′,5′-monophosphate on p70 ribosomal S6 kinase
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DOI：
10.1210/en.139.4.1991
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发表时间：
1998-04-01
期刊：
影响因子：
4.8
通讯作者：
Meinkoth, JL
中科院分区：
文献类型：
--
作者：
Cass, LA;Meinkoth, JL
cAMP对促有丝分裂信号通路发挥不同的作用。在许多细胞中，cAMP抑制生长因子刺激的MAPK活性和增殖。在其他情况下，cAMP促进生长。TSH通过升高甲状腺滤泡细胞中的cAMP来刺激增殖。这种促有丝分裂途径依赖于蛋白激酶A和Ras，但不依赖于Raf-1、促分裂原活化蛋白激酶激酶或促分裂原活化蛋白激酶。我们报告说，促甲状腺激素，通过cAMP，激活pp 70（s6 k），这种活动是必需的促甲状腺激素刺激的DNA合成。pp 70（s6 k）在cAMP介导的有丝分裂中的类似作用在次级大鼠雪旺细胞和Swiss 3 T3成纤维细胞中观察到，这两种额外的细胞类型对cAMP有生长反应。相反，cAMP升高不会激活NIH 3 T3或REF 52成纤维细胞中的pp 70（s6 k），在这些细胞中cAMP不能刺激增殖。总之，这些结果表明，pp 70（s6 k）在cAMP介导的增殖中起着重要和普遍的作用。
cAMP exerts differential effects on mitogenic signaling pathways. In many cells, cAMP inhibits growth factor-stimulated MAPK activity and proliferation. In others, cAMP promotes growth. TSH stimulates proliferation through elevations in cAMP in thyroid follicular cells. This mitogenic pathway is dependent upon both protein kinase A and Ras, but not upon Raf-1, mitogen-activated protein kinase kinase, or mitogen-activated protein kinase. We report that TSH, acting through cAMP, activates pp70(s6k) and that this activity is required for TSH-stimulated DNA synthesis. A similar role for pp70(s6k) in cAMP-mediated mitogenesis was observed in secondary rat Schwann cells and in Swiss3T3 fibroblasts, two additional cell types that respond to cAMP with growth. In contrast, cAMP elevation did not activate pp70(s6k) in NIH3T3 or REF52 fibroblasts, cells in which cAMP fails to stimulate proliferation. Together, these results suggest that pp70(s6k) plays an important and general role in cAMP-mediated proliferation.