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MEK1 and Protein Phosphatase 4 Coordinate Dictyostelium Development and Chemotaxis

机译:MEK1和蛋白磷酸酶4协调小球藻的发育和趋化性。

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The MEK and extracellular signal-regulated kinase/mitogen-activated protein kinase proteins are established regulators of multicellular development and cell movement. By combining traditional genetic and biochemical assays with a statistical analysis of global gene expression profiles, we discerned a genetic interaction between Dictyostelium discoideum mek1, smkA (named for its role in the suppression of the mek1? mutation), and pppC (the protein phosphatase 4 catalytic subunit gene). We found that during development and chemotaxis, both mek1 and smkA regulate pppC function. In other organisms, the protein phosphatase 4 catalytic subunit, PP4C, functions in a complex with the regulatory subunits PP4R2 and PP4R3 to control recovery from DNA damage. Here, we show that catalytically active PP4C is also required for development, chemotaxis, and the expression of numerous genes. The product of smkA (SMEK) functions as the Dictyostelium PP4R3 homolog and positively regulates a subset of PP4C's functions: PP4C-mediated developmental progression, chemotaxis, and the expression of genes specifically involved in cell stress responses and cell movement. We also demonstrate that SMEK does not control the absolute level of PP4C activity and suggest that SMEK regulates PP4C by controlling its localization to the nucleus. These data define a novel genetic pathway in which mek1 functions upstream of pppC-smkA to control multicellular development and chemotaxis.
机译:MEK和细胞外信号调节激酶/有丝分裂原激活的蛋白激酶蛋白是建立的多细胞发育和细胞运动的调节剂。通过将传统的遗传和生化分析与全球基因表达谱的统计分析相结合,我们发现了 Dictyostelium discoideum mek1,smkA (因其在抑制 mek1 < / em> ?突变)和 pppC (蛋白磷酸酶4催化亚基基因)。我们发现,在发育和趋化过程中, mek1 smkA 均调节 pppC 功能。在其他生物中,蛋白磷酸酶4催化亚基PP4C与调节亚基PP4R2和PP4R3形成复合物,以控制DNA损伤的恢复。在这里,我们显示了具有催化活性的PP4C也是发育,趋化性和众多基因表达所必需的。 smkA (SMEK)的产物起着 Dictyostelium PP4R3同源物的作用,并正调控PP4C的功能子集:PP4C介导的发育进程,趋化性和特定基因的表达参与细胞应激反应和细胞运动。我们还证明了SMEK不能控制PP4C活性的绝对水平,并建议SMEK通过控制PP4C定位于细胞核来调节PP4C。这些数据定义了一种新的遗传途径,其中 mek1 pppC - smkA 的上游起作用,以控制多细胞发育和趋化性。

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