RSK 激活
中文名称
通路描述
核糖体 S6 激酶 (RSK) 在人类中有四个等位基因：RPS6KA1 (RSK1)、RPS6KA2 (RSK3)、RPS6KA3 (RSK2) 和 RPS6KA6 (RSK4)，每个等位基因都有六个保守的磷酸化位点 (在 RPS6KA1 中，这些是丝氨酸残基 S221、S363 和 S380 以及苏氨酸残基 T359、T573 和 T732)。四个位点的磷酸化对于 RSK 的催化活性至关重要：S221、S363、S380 和 T573 (在 RPS6KA1 中)。RSK 的磷酸化和激活主要发生在细胞膜上，但也可能发生在细胞质和细胞核中。ERKs (MAPK1 和 MAPK3)，作为 RAS 信号下游激活，在 RPS6KA1 中磷酸化 RSK 的苏氨酸和丝氨酸残基 T359、S363 和 T573。ERK 的磷酸化使 RSK 在丝氨酸残基 S380 和苏氨酸残基 T732 (在 RPS6KA1 中) 发生自磷酸化。RSK 的磷酸化由 PDPK1 (PDK1) 在丝氨酸残基 S221 (在 RPS6KA1 中) 处磷酸化，对于 RSK 的完全激活和 RSK 底物的磷酸化是必要的 (Anjum 和 Blenis 2012)。RSK4 与其他 RSK 不同，因为它在没有生长因子的情况下表现出高水平的持续磷酸化和活性，尽管它仍然对生长因子和 ERK 活性敏感 (Dummler 等，2005)。RSK2 在具有高突触活性的脑区中高度表达。RSK2 突变是 Coffin-Lowry 综合征 (CLS) 的病因，该综合征以认知障碍和骨骼异常为特征 (Zeniou 等，2002)。
英文描述
RSK activation Ribosomal S6 kinase (RSK) has four isoforms in humans, RPS6KA1 (RSK1), RPS6KA2 (RSK3), RPS6KA3 (RSK2) and RPS6KA6 (RSK4), and each of the isoforms have six conserved phosphorylation sites (in RPS6KA1, these are serine residues S221, S363 and S380 and threonine residues T359, T573 and T732). Phosphorylation at four of these residues appears to be critically important for the catalytic activity of RSKs: S221, S363, S380 and T573 (in RPS6KA1).
Phosphorylation and activation of RSKs primarily occurs at the plasma membrane, but can occur in the cytoplasm and in the nucleus. ERKs (MAPK1 and MAPK3), activated downstream of RAS signaling, phosphorylate RSKs on threonine and serine residues T359, S363 and T573 (in RPS6KA1). Phosphorylation by ERKs enables autophosphorylation of RSKs on serine residue S380 and threonine residue T732 (in RPS6KA1). Phosphorylation of RSKs by PDPK1 (PDK1) at serine residue S221 (in RPS6KA1) is necessary for the full activation of RSKs and phosphorylation of RSK substrates (reviewed by Anjum and Blenis 2012). RSK4 differs from other RSKs because it shows high level of constitutive phosphorylation and activity in the absence of growth factors, although it is still responsive to growth factors and ERK activity (Dummler et al. 2005).
RSKs, especially RSK2, are highly expressed in brain regions with high synaptic activity. RSK2 mutations are the underlying cause of Coffin-Lowry syndrome (CLS), which is characterized by cognitive impairment and skeletal anomalies (Zeniou et al. 2002).
Phosphorylation and activation of RSKs primarily occurs at the plasma membrane, but can occur in the cytoplasm and in the nucleus. ERKs (MAPK1 and MAPK3), activated downstream of RAS signaling, phosphorylate RSKs on threonine and serine residues T359, S363 and T573 (in RPS6KA1). Phosphorylation by ERKs enables autophosphorylation of RSKs on serine residue S380 and threonine residue T732 (in RPS6KA1). Phosphorylation of RSKs by PDPK1 (PDK1) at serine residue S221 (in RPS6KA1) is necessary for the full activation of RSKs and phosphorylation of RSK substrates (reviewed by Anjum and Blenis 2012). RSK4 differs from other RSKs because it shows high level of constitutive phosphorylation and activity in the absence of growth factors, although it is still responsive to growth factors and ERK activity (Dummler et al. 2005).
RSKs, especially RSK2, are highly expressed in brain regions with high synaptic activity. RSK2 mutations are the underlying cause of Coffin-Lowry syndrome (CLS), which is characterized by cognitive impairment and skeletal anomalies (Zeniou et al. 2002).
所含基因
7 个基因