alpha(1B)- and alpha(1D)-Adrenergic receptors exhibit different requirements for agonist and mitogen-activated protein kinase activation to regulate growth responses in rat 1 fibroblasts.
alpha(1B)- and alpha(1D)-Adrenergic receptors exhibit different requirements for agonist and mitogen-activated protein kinase activation to regulate growth responses in rat 1 fibroblasts.
复制标题
DOI：
--
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
B. Waldrop;Diana M. Mastalerz;M. Piascik;G. Post
中科院分区：
文献类型：
--
作者：
B. Waldrop;Diana M. Mastalerz;M. Piascik;G. Post
我们比较了稳定表达α（1B）-肾上腺素能受体（AR）或α（1D）-AR亚型的大鼠1型成纤维细胞的DNA复制、蛋白质生物合成和丝裂原活化蛋白激酶（MAPK）活性。α（1B）-AR和α（1D）-AR的激活均抑制DNA合成（通过[（3）H]胸苷掺入进行评估）。相反，这两种受体刺激蛋白质生物合成（通过[（35）S]蛋氨酸掺入测定）和激活细胞外信号调节激酶（ERK）1/2。重要的是，这些反应对α（1B）-AR是激动剂依赖性的，但对α（1D）-AR是激动剂非依赖性的。α（1B）-AR的激动剂激活导致p38激酶活性增加，但不导致c-Jun NH（2）-末端激酶（JNK）活性增加，而α（1D）-AR激活JNK但不激活p38激酶。与ERK 1/2不同，JNK活性在α（1D）-AR细胞中通过激动剂处理而增加。ERK 1/2通路抑制剂PD 98059对苯肾上腺素介导的DNA合成抑制没有影响，但阻断了两种受体介导的蛋白质生物合成。p38激酶抑制剂SB 203580阻断了α（1B）-AR对表达α（1B）-AR的细胞中[（3 H）]胸苷和[（35）S]甲硫氨酸掺入的影响，但对α（1D）-AR介导的生长反应没有影响，这与α（1D）-AR不能激活p38激酶一致。因此，α（1B）-和α（1D）-AR介导相似的生长反应，但在所涉及的MAPK家族成员和对激动剂的需求方面有所不同。
We compared DNA replication, protein biosynthesis, and mitogen-activated protein kinase (MAPK) activity in Rat 1 fibroblasts stably expressing either the alpha(1B)-adrenergic receptor (AR) or alpha(1D)-AR subtypes. Activation of both the alpha(1B)-AR and alpha(1D)-AR inhibited DNA synthesis (as assessed by [(3)H]thymidine incorporation). In contrast, both receptors stimulated protein biosynthesis (as measured by [(35)S]methionine incorporation) and activated extracellular signal-regulated kinase (ERK)1/2. Importantly, these responses were agonist-dependent for the alpha(1B)-AR, but were agonist-independent for the alpha(1D)-AR. Agonist activation of the alpha(1B)-AR resulted in increased p38 kinase activity, but not c-Jun NH(2)-terminal kinase (JNK) activity, whereas the alpha(1D)-AR activated JNK but not p38 kinase. Unlike ERK1/2, JNK activity was increased by agonist treatment in the alpha(1D)-AR cells. An ERK1/2-pathway inhibitor PD98059 had no effect on phenylephrine-mediated inhibition of DNA synthesis in either cell line but blocked protein biosynthesis mediated by both receptors. The p38 kinase inhibitor SB203580 blocked alpha(1B)-AR effects on [(3)H]thymidine and [(35)S]methionine incorporation in alpha(1B)-AR-expressing cells, but had no effect on alpha(1D)-AR-mediated growth responses, consistent with the inability of the alpha(1D)-AR to activate p38 kinase. Therefore, alpha(1B)- and alpha(1D)-ARs mediated similar growth responses but differ with respect to the MAPK family member involved and the requirement for agonist.