The Fat1 cadherin integrates vascular smooth muscle cell growth and migration signals.
The Fat1 cadherin integrates vascular smooth muscle cell growth and migration signals.
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DOI：
10.1083/jcb.200508121
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发表时间：
2006-05-08
期刊：
影响因子：
--
通讯作者：
Sibinga NE
中科院分区：
文献类型：
--
作者：
Hou R;Liu L;Anees S;Hiroyasu S;Sibinga NE
钙粘蛋白超家族蛋白在血管平滑肌细胞(VSMC)生物学中的意义尚不明确。在这里，我们描述了最近对Fat1原钙粘附素的研究。动脉损伤或生长因子刺激后，VSMCs中Fat1的表达显著增加。Fat1基因敲除可减少VSMC在体外的迁移，但令人惊讶的是，它能促进细胞周期蛋白D1的表达和增殖。尽管与经典钙粘附素有有限的相似性，但Fat1胞内域(Fat1IC)与β-连环蛋白相互作用，抑制其核定位和转录活性。Fat1经历了切割，Fat1IC物种定位于细胞核；然而，截短的Fat1IC蛋白对细胞周期蛋白D1启动子的抑制相当于它们存在于核外，这反对核Fat1IC抑制β-连环蛋白依赖的转录。这些发现扩展了最近对FAT1和其他类型细胞迁移的观察，并首次证明了它的抗增殖活性和与β-连环蛋白的相互作用。由于Fat1是在动脉损伤后诱导的，它可能通过促进迁移和限制增殖来控制血管重塑中心的VSMC功能。
The significance of cadherin superfamily proteins in vascular smooth muscle cell (VSMC) biology is undefined. Here we describe recent studies of the Fat1 protocadherin. Fat1 expression in VSMCs increases significantly after arterial injury or growth factor stimulation. Fat1 knockdown decreases VSMC migration in vitro, but surprisingly, enhances cyclin D1 expression and proliferation. Despite limited similarity to classical cadherins, the Fat1 intracellular domain (Fat1IC) interacts with β-catenin, inhibiting both its nuclear localization and transcriptional activity. Fat1 undergoes cleavage and Fat1IC species localize to the nucleus; however, inhibition of the cyclin D1 promoter by truncated Fat1IC proteins corresponds to their presence outside the nucleus, which argues against repression of β-catenin–dependent transcription by nuclear Fat1IC. These findings extend recent observations about Fat1 and migration in other cell types, and demonstrate for the first time its anti-proliferative activity and interaction with β-catenin. Because it is induced after arterial injury, Fat1 may control VSMC functions central to vascular remodeling by facilitating migration and limiting proliferation.
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DOI：
10.1083/jcb.125.6.1341
发表时间：
1994-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Näthke IS;Hinck L;Swedlow JR;Papkoff J;Nelson WJ
通讯作者：
Nelson WJ
影响因子：
2.7
作者：
Hedgepeth, CM;Conrad, LJ;Klein, PS
通讯作者：
Klein, PS
影响因子：
4.8
作者：
Castillejo-López, C;Arias, WM;Baumgartner, S
通讯作者：
Baumgartner, S
影响因子：
7.8
作者：
MULLER, WA;GIMBRONE, MA
通讯作者：
GIMBRONE, MA
影响因子：
11.4
作者：
Moeller, MJ;Soofi, A;Holzman, LB
通讯作者：
Holzman, LB