Glutamate-stimulated activation of DNA synthesis via mitogen-activated protein kinase in primary astrocytes: involvement of protein kinase C and related adhesion focal tyrosine kinase.
Glutamate-stimulated activation of DNA synthesis via mitogen-activated protein kinase in primary astrocytes: involvement of protein kinase C and related adhesion focal tyrosine kinase.
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原代星形胶质细胞中谷氨酸通过丝裂原激活蛋白激酶刺激 DNA 合成的激活：蛋白激酶 C 和相关粘附局灶酪氨酸激酶的参与。
DOI：
10.1046/j.1471-4159.2000.0741931.x
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发表时间：
2000
影响因子：
4.7
通讯作者：
Avraham,S
中科院分区：
文献类型：
--
作者：
Schinkmann,KA;Kim,TA;Avraham,S
翻译后摘要：谷氨酸是中枢神经系统中的主要兴奋性神经递质。虽然它在神经元中的作用已被广泛研究，但对其在星形胶质细胞中的功能知之甚少。我们研究了谷氨酸对原代星形胶质细胞信号通路的影响。我们发现酪氨酸激酶相关的粘附灶酪氨酸激酶（RAFTK）以时间和剂量依赖性方式对谷氨酸产生酪氨酸磷酸化反应。这种磷酸化是百日咳毒素（PTX）敏感的，可以通过消耗细胞内储存的Ca 2+来减弱。RAFTK酪氨酸磷酸化主要由I/II类代谢型谷氨酸受体介导，并依赖于蛋白激酶C（PKC）激活。原代星形胶质细胞的谷氨酸处理也导致有丝分裂原活化蛋白激酶[细胞外信号相关激酶1/2（ERK 1/2）]活性显著增加。与RAFTK磷酸化类似，ERK 1/2活化对PTX敏感，可通过细胞内Ca 2+耗竭和PKC抑制而减弱，表明RAFTK可能介导ERK 1/2的谷氨酸依赖性活化。此外，我们证明，谷氨酸刺激的初级星形胶质细胞导致DNA合成显着增加。谷氨酸刺激的DNA合成是PTX敏感的，并且可以被MAP激酶激酶抑制剂PD 98059抑制，这表明在原代星形胶质细胞中，谷氨酸可能通过RAFTK和MAP激酶发出信号以促进DNA合成和细胞增殖。
Abstract:Glutamate is the major excitatory neurotransmitter in the CNS. Although its role in neurons has been studied extensively, little is known about its function in astrocytes. We studied the effects of glutamate on signaling pathways in primary astrocytes. We found that the tyrosine kinase related adhesion focal tyrosine kinase (RAFTK) is tyrosine phosphorylated in response to glutamate in a time‐ and dose‐dependent manner. This phosphorylation was pertussis toxin (PTX) sensitive and could be attenuated by the depletion of Ca2+from intracellular stores. RAFTK tyrosine phosphorylation was mediated primarily by class I/II metabotropic glutamate receptors and depends on protein kinase C (PKC) activation. Glutamate treatment of primary astrocytes also results in a significant increase in the activity of the mitogen‐activated protein kinases [extracellular signal‐related kinases 1/2 (ERK1/2)]. Like RAFTK phosphorylation, ERK1/2 activation is PTX sensitive and can be attenuated by the depletion of intracellular Ca2+and by PKC inhibition, suggesting that RAFTK might mediate the glutamate‐dependent activation of ERK1/2. Furthermore, we demonstrated that glutamate stimulation of primary astrocytes leads to a significant increase in DNA synthesis. Glutamate‐stimulated DNA synthesis is PTX sensitive and can be inhibited by the MAP kinase kinase inhibitor PD98059, suggesting that in primary astrocytes, glutamate might signal via RAFTK and MAP kinase to promote DNA synthesis and cell proliferation.