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Altered serine/threonine kinase activity in schizophrenia

机译：精神分裂症的丝氨酸/苏氨酸激酶活性改变

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Converging evidence implicates alterations in multiple signaling pathways in the etiology of schizophrenia. Previously, these studies were limited to the analysis of one or a few phosphoproteins at a time. Here, we use a novel kinase array platform to simultaneously investigate the convergence of multiple signaling cascades implicated in schizophrenia. This technology uses consensus peptide substrates to assess activity levels of a large number (> 100) of serine/threonine protein kinases. 19 peptide substrates were differentially phosphorylated (>15% change) in the frontal cortex in schizophrenia. These peptide substrates were examined using Ingenuity Pathway Analysis to group them according to the functions and to identify processes most likely affected in schizophrenia. Pathway analysis placed 14 of the 19 peptides into cellular homeostatic pathways, 10 into pathways governing cytoskeletal organization, and 8 into pathways governing ion homeostasis. These data are the first to simultaneously investigate comprehensive changes in signaling cascades in a severe psychiatric disorder. The examination of kinase activity in signaling pathways may facilitate the identification of novel substrates for drug discovery and the development of safer and more effective pharmacological treatment for schizophrenia.
机译：越来越多的证据表明精神分裂症的病因学中多个信号传导途径发生了改变。以前，这些研究仅限于一次分析一种或几种磷蛋白。在这里，我们使用一种新型的激酶阵列平台来同时研究精神分裂症中牵连的多个信号级联的收敛性。该技术使用共有肽底物来评估大量（> 100）丝氨酸/苏氨酸蛋白激酶的活性水平。精神分裂症的额叶皮层中19种肽底物被差异磷酸化（变化> 15％）。使用Ingenuity Pathway Analysis检查这些肽底物，以根据功能将其分组并确定最可能在精神分裂症中受影响的过程。途径分析将19种肽中的14种置于细胞稳态途径中，将10种置于控制细胞骨架组织的途径中，将8种置于控制离子稳态的途径中。这些数据是第一个同时研究严重精神病患者信号级联反应全面变化的数据。信号通路中激酶活性的检查可能有助于鉴定新的底物用于药物发现以及开发用于精神分裂症的更安全，更有效的药理学治疗方法。

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