Growth Factor Activity of Endothelin-1 in Primary Astrocytes Mediated by Adhesion-Dependent and -Independent Pathways
Growth Factor Activity of Endothelin-1 in Primary Astrocytes Mediated by Adhesion-Dependent and -Independent Pathways
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原代星形胶质细胞内皮素 1 的生长因子活性由粘附依赖性和非依赖性途径介导
DOI：
10.1523/jneurosci.17-16-06203.1997
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
P. Couraud
中科院分区：
文献类型：
--
作者：
S. Cazaubon;N. Chaverot;I. Romero;J. Girault;P. Adamson;A. Strosberg;P. Couraud
内皮素-1 (ET-1) 已被证明可通过刺激细胞外信号调节激酶 (ERK) 途径诱导原代星形胶质细胞中的 DNA 合成。为了阐明星形胶质细胞贴壁依赖性生长的机制，研究了细胞粘附和 ERK 激活之间的关系。据报道，ET-1 促进应力纤维和粘着斑的形成以及粘着斑激酶 (FAK) 和桩蛋白的酪氨酸磷酸化，以及 Src 激活和磷酸化 FAK 与 Grb2 的结合。用细胞松弛素 D 或 C3 转移酶（分别抑制肌动蛋白聚合或 Rho 活性）预处理星形胶质细胞，可防止 ET-1 刺激后 Src、FAK 和桩蛋白的激活/磷酸化；相比之下，ERK 通路并未受到显着影响。在星形胶质细胞重新接种到聚-L-鸟氨酸预涂培养皿上 10 和 60 分钟后，也观察到了 FAK/Src 和 ERK 途径的这种差异激活。总的来说，这些发现表明 FAK 和 Src 的激活依赖于肌动蛋白细胞骨架的完整性、Rho 激活和细胞外基质的粘附，而 ERK 激活独立于这些细胞内事件，并且似乎与新鉴定的蛋白酪氨酸激酶 PYK2 的激活相关。然而，在用细胞松弛素 D 或 C3 转移酶预处理的星形胶质细胞中，ET-1 诱导的 DNA 合成显着减少。这项研究证明了 FAK/Src 的 Rho 和粘附依赖性激活，它与 PYK2/ERK 的粘附非依赖性激活协同作用，在 ET-1 刺激的星形胶质细胞中进行 DNA 合成。
Endothelin-1 (ET-1) has been shown to induce DNA synthesis in primary astrocytes by stimulating the extracellular signal-regulated kinase (ERK) pathway. To clarify the mechanisms responsible for the anchorage-dependent growth of astrocytes, the relationships between cell adhesion and ERK activation were investigated. Here it is reported that ET-1 promotes the formation of stress fibers and focal adhesions and the tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin, as well as Src activation and association of phosphorylated FAK with Grb2. Pretreatment of astrocytes with cytochalasin D or C3-transferase, which inhibits actin polymerization or Rho activity, respectively, prevented the activation/phosphorylation of Src, FAK, and paxillin after ET-1 stimulation; by contrast, the ERK pathway was not significantly affected. This differential activation of FAK/Src and ERK pathways was also observed with astrocytes 10 and 60 min after replating on poly-l-ornithine-precoated dishes. Collectively, these findings indicate that activation of FAK and Src is dependent on actin cytoskeleton integrity, Rho activation, and adhesion to extracellular matrix, whereas ERK activation is independent of these intracellular events and seems to correlate with activation of the newly identified protein tyrosine kinase PYK2. Induction of DNA synthesis by ET-1, however, was reduced dramatically in astrocytes pretreated with either cytochalasin D or C3-transferase. This study provides a demonstration of Rho- and adhesion-dependent activation of FAK/Src, which collaborates with adhesion-independent activation of PYK2/ERK for DNA synthesis in ET-1-stimulated astrocytes.
DOI：
10.1073/pnas.87.6.2359
发表时间：
1990-03-01
影响因子：
11.1
作者：
MACCUMBER, MW;ROSS, CA;SNYDER, SH
通讯作者：
SNYDER, SH
血小板中 pp125FAK 的酪氨酸磷酸化需要通过整合素和激动剂受体协调信号传导。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Shattil,SJ;Haimovich,B;Cunningham,M;Lipfert,L;Parsons,JT;Ginsberg,MH;Brugge,JS
通讯作者：
Brugge,JS