PAK1-mediated activation of ERK1/2 regulates lamellipodial dynamics.
PAK1-mediated activation of ERK1/2 regulates lamellipodial dynamics.
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DOI：
10.1242/jcs.027680
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发表时间：
2008-11-15
影响因子：
4
通讯作者：
Ridley AJ
中科院分区：
文献类型：
--
作者：
Smith SD;Jaffer ZM;Chernoff J;Ridley AJ
PAK 1是丝氨酸/苏氨酸激酶的p21激活激酶（PAK）家族的成员，其由Rho GTP酶Rac和Cdc 42激活，并且涉及调节形态极性、细胞迁移和粘附。在这里，我们调查的功能PAK 1在细胞运动中使用来自PAK 1-null小鼠的巨噬细胞。我们发现，CSF-1，巨噬细胞化学引诱物，短暂刺激PAK 1和MAPK激活，并且MAPK激活在PAK 1 −/−巨噬细胞中减少。PAK 1调节板状伪足延伸的动力学，因为细胞响应于粘附而扩散，但对于巨噬细胞迁移或对CSF-1的趋化性不是必需的。粘附后，PAK 1 −/−巨噬细胞比野生型巨噬细胞扩散更快，并且具有更多但更不稳定的板状伪足。在粘附过程中，PAK 1 −/−巨噬细胞中的ERK 1/2活性降低，抑制野生型巨噬细胞中的ERK 1/2活化足以增加铺展面积并模拟PAK 1 −/−巨噬细胞的板脂动力学。总之，这些数据表明PAK 1通过ERK 1/2信号调节片状脂质体稳定性。
PAK1 is a member of the p21-activated kinase (PAK) family of serine/threonine kinases that are activated by the Rho GTPases Rac and Cdc42 and are implicated in regulating morphological polarity, cell migration and adhesion. Here we investigate the function of PAK1 in cell motility using macrophages derived from PAK1-null mice. We show that CSF-1, a macrophage chemoattractant, transiently stimulates PAK1 and MAPK activation, and that MAPK activation is reduced in PAK1−/− macrophages. PAK1 regulates the dynamics of lamellipodium extension as cells spread in response to adhesion but is not essential for macrophage migration or chemotaxis towards CSF-1. Following adhesion, PAK1−/− macrophages spread more rapidly than wild-type macrophages and have more but less stable lamellipodia. ERK1/2 activity was reduced in PAK1−/− macrophages during adhesion, and inhibition of ERK1/2 activation in wild-type macrophages was sufficient to increase the spread area and mimic the lamellipodial dynamics of PAK1−/− macrophages. Together, these data indicate that PAK1 signals via ERK1/2 to regulate lamellipodial stability.
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