Depolarization-induced signaling to Ras, Rap1 and MAPKs in cortical neurons
Depolarization-induced signaling to Ras, Rap1 and MAPKs in cortical neurons
复制标题
DOI：
10.1016/j.molbrainres.2003.08.020
复制
发表时间：
2003-11-06
期刊：
影响因子：
--
通讯作者：
Sturani, E
中科院分区：
文献类型：
--
作者：
Baldassa, S;Zippel, R;Sturani, E
在神经元中，膜去极化触发多效性信号传导，其包括小GTP酶Ras和Rap 1以及促分裂原活化蛋白激酶（MAPK）Erk 1/2的活化。我们已经研究了在小鼠培养的皮层神经元中调节这些事件的细胞内信号传导机制。我们发现，去极化诱导Ras和Rap1的激活，虽然具有不同的动力学：Ras激活是强而快，而Rap1激活是慢而弱。阻断钙调蛋白影响Ras和Rap1的GTP负载并阻止MAPK反应。此外，蛋白激酶A（PKA）活性是去极化诱导的Rap1激活和完全Erk刺激所必需的，但不参与Ras的激活。这种PKA依赖性Rap1激活不需要Src家族激酶，但与Ras相反，对染料木素敏感，表明参与了酪氨酸激酶依赖性机制。我们的数据为神经元中Ras和Rap1激活的调节提供了新的见解。(C)2003 Elsevier B.V.保留所有权利。
In neurons, membrane depolarization triggers pleiotropic signaling which includes the activation of the small GTPases, Ras and Rap 1, and the mitogen-activated protein kinases (MAPKs) Erk1/2. We have studied the intracellular signaling mechanisms which regulate these events in mouse-cultured cortical neurons. We show that depolarization induces activation of both Ras and Rap1, although with different kinetics: Ras activation is strong and fast while Rap1 activation is slower and weaker. Blockade of calmodulin affects the GTP-loading of Ras and Rap1 and prevents the MAPK response. Moreover, protein kinase A (PKA) activity is required for depolarization- induced Rap1 activation and full Erk stimulation, but is not involved in that of Ras. This PKA-dependent Rap1 activation does not require Src family kinases, but, in contrast to Ras, is sensitive to genistein, indicating the involvement of a tyrosine kinase-dependent mechanism. Our data provide new insights into the regulation of Ras and Rap1 activation in neurons. (C) 2003 Elsevier B.V. All rights reserved.