c-Src regulates the simultaneous rearrangement of actin cytoskeleton, p190RhoGAP, and p120RasGAP following epidermal growth factor stimulation.
c-Src regulates the simultaneous rearrangement of actin cytoskeleton, p190RhoGAP, and p120RasGAP following epidermal growth factor stimulation.
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DOI：
10.1083/jcb.130.2.355
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发表时间：
1995-07
影响因子：
7.8
通讯作者：
PARSONS, SJ
中科院分区：
文献类型：
--
作者：
CHANG, JH;GILL, S;SETTLEMAN, J;PARSONS, SJ
对过表达野生型和显性阴性c-Src变体的C3H10T1/2小鼠成纤维细胞的分析表明，在egf诱导的有丝分裂发生中需要c-Src。与c-Src变异体增强或抑制egf依赖性DNA合成能力相关的是多种细胞蛋白的磷酸酪氨酸含量，包括p190- RhoGAP，一种被认为通过调节小GTP结合蛋白Rho的活性来调节生长因子诱导的肌动蛋白细胞骨架重塑的蛋白质。由于p190的体内磷酸酪氨酸含量随活性c-Src水平而变化，而不随EGF处理而变化，因此p190被认为是c-Src的首选底物。为了确定p190的酪氨酸磷酸化（通过c-Src）是否会影响EGF依赖性肌动蛋白重塑，我们使用常规和共聚焦免疫荧光显微镜检查了EGF刺激或未刺激的10T1/2 Neo对照细胞和稳定过表达野生型（K+）或激酶缺陷型（K-） c-Src的细胞内p190、肌动蛋白和p120RasGAP的分布。我们发现，在所有细胞系中，EGF诱导p190和RasGAP迅速而短暂地凝聚成细胞质的弧形结构。然而，与对照细胞相比，在K+细胞中，出现弧线的细胞率和细胞数量增加。相反，K细胞表现出延迟形成电弧和减少形成电弧的细胞数量。在所有三种细胞系中，egf诱导的肌动蛋白应激纤维的拆卸和重组发生的动力学和频率与p190和RasGAP重排相同。这些结果，连同p190固有的Rho- gap活性和Rho调节肌动蛋白应激纤维形成的能力，表明c-Src通过磷酸化p190调节egf依赖性肌动蛋白细胞骨架重组。
Analysis of C3H10T1/2 murine fibroblasts overexpressing wild type and dominant negative variants of c-Src has demonstrated a requirement for c-Src in EGF-induced mitogenesis. Correlating with the ability of c-Src variants to potentiate or inhibit EGF-dependent DNA synthesis is the phosphotyrosine content of multiple cellular proteins, including p190- RhoGAP, a protein thought to regulate growth factor-induced actin cytoskeleton remodeling by modulating the activity of the small GTP binding protein, Rho. Because the in vivo phosphotyrosine content of p190 varies with the level of active c-Src and not with EGF treatment, p190 is considered to be a preferred substrate of c-Src. To determine whether tyrosyl phosphorylation of p190 (by c-Src) could influence EGF- dependent actin remodeling, we used conventional and confocal immunofluorescence microscopy to examine the intracellular distribution of p190, actin, and p120RasGAP in EGF-stimulated or unstimulated 10T1/2 Neo control cells and cells that stably overexpress wild-type (K+) or kinase-defective (K-) c-Src. We found that in all cell lines, EGF induced a rapid and transient condensation of p190 and RasGAP into cytoplasmic, arclike structures. However, in K+ cells the rate of appearance and number of cells exhibiting arcs increased when compared with control cells. Conversely, K- cells exhibited delayed arc formation and a reduction in number of cells forming arcs. EGF-induced actin stress fiber disassembly and reassembly occurred with the same kinetics and frequency as did p190 and RasGAP rearrangements in all three cell lines. These results, together with the documented Rho-GAP activity intrinsic to p190 and the ability of Rho to modulate actin stress fiber formation, suggest that c-Src regulates EGF-dependent actin cytoskeleton reorganization through phosphorylation of p190.
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DOI：
10.1083/jcb.119.2.349
发表时间：
1992-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
den Hartigh JC;van Bergen en Henegouwen PM;Verkleij AJ;Boonstra J
通讯作者：
Boonstra J
影响因子：
16.2
作者：
IGNELZI, MA;MILLER, DR;MANESS, PF
通讯作者：
MANESS, PF
影响因子：
11.4
作者：
BLUMEJENSEN, P;CLAESSONWELSH, L;HELDIN, CH
通讯作者：
HELDIN, CH
DOI：
10.1083/jcb.123.1.173
发表时间：
1993-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cao LG;Fishkind DJ;Wang YL
通讯作者：
Wang YL
影响因子：
64.8
作者：
ELLIS, C;MORAN, M;PAWSON, T
通讯作者：
PAWSON, T