Insulin-like growth factor-1 (IGF-1) induces the activation/phosphorylation of Akt kinase and cAMP response element-binding protein (CREB) by activating different signaling pathways in PC12 cells.
Insulin-like growth factor-1 (IGF-1) induces the activation/phosphorylation of Akt kinase and cAMP response element-binding protein (CREB) by activating different signaling pathways in PC12 cells.
复制标题
DOI：
10.1186/1471-2202-7-51
复制
发表时间：
2006-06-22
期刊：
影响因子：
2.4
通讯作者：
Quirion R
中科院分区：
文献类型：
--
作者：
Zheng WH;Quirion R
胰岛素样生长因子-1（IGF-1）是一种在神经元和非神经元细胞中具有多种功能的多肽生长因子。IGF-1通过激活包括Akt激酶（一种对细胞存活至关重要的丝氨酸/苏氨酸激酶）在内的多种信号通路发挥抗凋亡和其他功能。核转录因子cAMP反应元件结合蛋白（CREB）也可能参与其中，尽管这两种蛋白在IGF-1受体信号传导和保护中的关系尚不清楚，尤其是在神经元细胞中。IGF-1以浓度和时间依赖性方式通过激活不同的信号通路诱导PC 12细胞中Akt和CREB的激活/磷酸化。IGF-1诱导Akt持续磷酸化，而CREB仅出现短暂磷酸化。Akt的磷酸化由PI 3激酶途径介导，而CREB的磷酸化依赖于MAPK激酶和p38 MAPK的激活。此外，PKC的刺激减弱了IGF-1诱导的Akt磷酸化，而CREB的磷酸化增强。使用各种激酶抑制剂的存活测定表明，Akt和CREB的活化/磷酸化有助于IGF-1介导的PC 12细胞中的细胞存活。这些数据表明，IGF-1诱导激活Akt和CREB使用不同的途径在PC 12细胞。
Insulin-like growth factor-1 (IGF-1) is a polypeptide growth factor with a variety of functions in both neuronal and non-neuronal cells. IGF-1 plays anti-apoptotic and other functions by activating multiple signaling pathways including Akt kinase, a serine/threonine kinase essential for cell survival. The nuclear transcription factor cAMP response element-binding protein (CREB) may also be involved although relationships between these two proteins in IGF-1 receptor signaling and protection is not clear, especially in neuronal cells. IGF-1, in a concentration- and time-dependent manner, induces the activation/phosphorylation of Akt and CREB in PC12 cells by activating different signaling pathways. IGF-1 induced a sustained phosphorylation of Akt while only a transient one was seen for CREB. The phosphorylation of Akt is mediated by the PI3 kinase pathway while that of CREB is dependent on the activation of both MAPK kinase and p38 MAPK. Moreover, the stimulation of PKC attenuated the phosphorylation of Akt induced by IGF-1 while enhancing that of CREB. Survival assays with various kinase inhibitors suggested that the activation/phosphorylation of both Akt and CREB contributes to IGF-1 mediated cell survival in PC12 cells. These data suggest that IGF-1 induced the activation of Akt and CREB using distinct pathways in PC12 cells.
登录
查看更多内容
影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
3.5
作者：
Arthur, JSC;Cohen, P
通讯作者：
Cohen, P
DOI：
10.1590/s0100-879x1997000800009
发表时间：
1997-08-01
影响因子：
2.3
作者：
Bevilaqua, L;Ardenghi, P;Izquierdo, I
通讯作者：
Izquierdo, I
影响因子：
4.8
作者：
Du, KY;Montminy, M
通讯作者：
Montminy, M
DOI：
10.1016/s0169-328x(98)00122-3
发表时间：
1998-08-31
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Beilharz, EJ;Russo, VC;Scheepens, A
通讯作者：
Scheepens, A