Drosophila pico and its mammalian ortholog lamellipodin activate serum response factor and promote cell proliferation.
Drosophila pico and its mammalian ortholog lamellipodin activate serum response factor and promote cell proliferation.
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DOI：
10.1016/j.devcel.2008.09.020
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发表时间：
2008-11
影响因子：
11.8
通讯作者：
Bennett, Daimark
中科院分区：
文献类型：
--
作者：
Lyulcheva, Ekaterina;Taylor, Eleanor;Michael, Magdalene;Vehlow, Anne;Tan, Shengjiang;Fletcher, Adam;Krause, Matthias;Bennett, Daimark
β-10/RIAM/lamellipodin（MRL）蛋白将活化的Ras-GTP酶与肌动蛋白调节性Ena/VASP蛋白连接以诱导细胞骨架动力学和细胞运动性的局部变化。MRL蛋白改变单体（G）：丝状（F）肌动蛋白的比例，但这些变化的影响尚未得到充分认识。我们在这里报告，果蝇MRL直系同源，皮科，是组织和有机体生长所需的。皮科水平的降低导致细胞分裂速率降低、生长迟缓、G：F肌动蛋白比率增加和致死率。相反，皮科过表达减少G：F肌动蛋白的比例，促进组织过度生长的表皮生长因子（EGF）受体（EGFR）依赖的方式。因此，在HeLa细胞中，EGF诱导的增殖需要lamellipodin。我们发现，皮科和lamellipodin共享的能力，激活血清反应因子（SRF），一种转录因子，响应减少G：F-肌动蛋白比率通过其辅因子Mal。遗传学数据表明，Mal/SRF水平是重要的微微介导的组织生长。我们认为MRL蛋白通过肌动蛋白动力学的变化将EGFR激活与促有丝分裂SRF信号传导联系起来。
MIG-10/RIAM/lamellipodin (MRL) proteins link activated Ras-GTPases with actin regulatory Ena/VASP proteins to induce local changes in cytoskeletal dynamics and cell motility. MRL proteins alter monomeric (G):filamentous (F) actin ratios, but the impact of these changes had not been fully appreciated. We report here that the Drosophila MRL ortholog, pico, is required for tissue and organismal growth. Reduction in pico levels resulted in reduced cell division rates, growth retardation, increased G:F actin ratios and lethality. Conversely, pico overexpression reduced G:F actin ratios and promoted tissue overgrowth in an epidermal growth factor (EGF) receptor (EGFR)-dependent manner. Consistently, in HeLa cells, lamellipodin was required for EGF-induced proliferation. We show that pico and lamellipodin share the ability to activate serum response factor (SRF), a transcription factor that responds to reduced G:F-actin ratios via its co-factor Mal. Genetics data indicate that mal/SRF levels are important for pico-mediated tissue growth. We propose that MRL proteins link EGFR activation to mitogenic SRF signaling via changes in actin dynamics.
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影响因子：
6.4
作者：
Eppert, K;Wunder, JS;Andrulis, IL
通讯作者：
Andrulis, IL
影响因子：
64.5
作者：
Böhni, R;Riesgo-Escovar, J;Hafen, E
通讯作者：
Hafen, E
影响因子：
64.8
作者：
Speck, O;Hughes, SC;Fehon, RG
通讯作者：
Fehon, RG
DOI：
10.1098/rspb.1990.0100
发表时间：
1990-10-22
影响因子：
4.7
作者：
DIAZBENJUMEA, FJ;GARCIABELLIDO, A
通讯作者：
GARCIABELLIDO, A
影响因子：
5.3
作者：
Rodriguez-Viciana, P;Sabatier, C;McCormick, F
通讯作者：
McCormick, F