Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase
Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase
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DOI：
10.1242/jcs.111146
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发表时间：
2012-12-01
影响因子：
4
通讯作者：
Tamanoi, Fuyuhiko
中科院分区：
文献类型：
--
作者：
Nakashima, Akio;Otsubo, Yoko;Tamanoi, Fuyuhiko
雷帕霉素靶蛋白（TOR）是一种进化上保守的丝氨酸/苏氨酸蛋白激酶，在真核生物的许多重要细胞过程中起着关键作用。在裂殖酵母裂殖酵母中，TOR复合物1（TORC 1）包括作为催化亚基的Tor 2，其通过感测营养可用性来管理细胞增殖和分化之间的切换。然而，很少有人知道TORC 1的直接目标，在裂变酵母中的营养依赖性TORC 1信号转导中发挥关键作用。在这里，我们报告，在分裂酵母，三个AGC激酶家族成员，命名为Psk 1，Sck 1和Sck 2，这表现出高度同源性与人类S6 K1，磷酸化在营养丰富的条件下，饥饿条件下去磷酸化。其中，Psk 1是核糖体蛋白S6磷酸化所必需的。此外，Psk 1磷酸化在体内以营养依赖性和雷帕霉素敏感性方式受TORC 1调节。Psk 1中的三个保守的调控基序（激活环、疏水基序和转向基序）被磷酸化，并且这些修饰是Psk 1活性所需的。特别地，疏水基序的磷酸化由TORC 1在体内和体外催化。Ksg 1是PDK 1的同源物，对活化环中的Psk 1磷酸化及其活性也很重要。TORC 1组分Pop3、Toc 1和Tco 89对Psk 1的调节是无效的，但破坏pop3（+）会导致TORC 1对雷帕霉素的敏感性增加。综上所述，这些结果提供了令人信服的证据，TORC 1/Psk 1/Rps 6构成了一个营养依赖的信号通路在裂变酵母。
Target of rapamycin (TOR), an evolutionarily conserved serine/threonine protein kinase, plays pivotal roles in several important cellular processes in eukaryotes. In the fission yeast Schizosaccharomyces pombe, TOR complex 1 (TORC1), which includes Tor2 as a catalytic subunit, manages the switch between cell proliferation and differentiation by sensing nutrient availability. However, little is known about the direct target of TORC1 that plays key roles in nutrient-dependent TORC1 signaling in fission yeast. Here we report that in fission yeast, three AGC kinase family members, named Psk1, Sck1 and Sck2, which exhibit high homology with human S6K1, are phosphorylated under nutrient-rich conditions and are dephosphorylated by starvation conditions. Among these, Psk1 is necessary for phosphorylation of ribosomal protein S6. Furthermore, Psk1 phosphorylation is regulated by TORC1 in nutrient-dependent and rapamycin-sensitive manners in vivo. Three conserved regulatory motifs (the activation loop, the hydrophobic and the turn motifs) in Psk1 are phosphorylated and these modifications are required for Psk1 activity. In particular, phosphorylation of the hydrophobic motif is catalyzed by TORC1 in vivo and in vitro. Ksg1, a homolog of PDK1, is also important for Psk1 phosphorylation in the activation loop and for its activity. The TORC1 components Pop3, Toc1 and Tco89, are dispensable for Psk1 regulation, but disruption of pop3(+) causes an increase in the sensitivity of TORC1 to rapamycin. Taken together, these results provide convincing evidence that TORC1/Psk1/Rps6 constitutes a nutrient-dependent signaling pathway in fission yeast.