BACKGROUND The non-receptor tyrosine kinase, SRMS (Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites) is a member of the BRK family kinases (BFKs) which represents an evolutionarily conserved relative of the Src family kinases (SFKs). Tyrosine kinases are known to regulate a number of cellular processes and pathways via phosphorylating substrate proteins directly and/or by partaking in signaling cross-talks leading to the indirect modulation of various signaling intermediates. In a previous study, we profiled the tyrosine-phosphoproteome of SRMS and identified multiple candidate substrates of the kinase. The broader cellular signaling intermediates of SRMS are unknown. METHODS In order to uncover the broader SRMS-regulated phosphoproteome and identify the SRMS-regulated indirect signaling intermediates, we performed label-free global phosphoproteomics analysis on cells expressing wild-type SRMS. Using computational database searching and bioinformatics analyses we characterized the dataset. RESULTS Our analyses identified 60 hyperphosphorylated (phosphoserine/phosphothreonine) proteins mapped from 140 hyperphosphorylated peptides. Bioinfomatics analyses identified a number of significantly enriched biological and cellular processes among which DNA repair pathways were found to be upregulated while apoptotic pathways were found to be downregulated. Analyses of motifs derived from the upregulated phosphosites identified Casein kinase 2 alpha (CK2α) as one of the major potential kinases contributing to the SRMS-dependent indirect regulation of signaling intermediates. CONCLUSIONS Overall, our phosphoproteomics analyses identified serine/threonine phosphorylation dynamics as important secondary events of the SRMS-regulated phosphoproteome with implications in the regulation of cellular and biological processes.

中文翻译：

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全球磷酸蛋白质组学分析确定了 SRMS 调节的二级信号中间体。

背景非受体酪氨酸激酶，SRMS（缺乏 C 端调节酪氨酸和 N 端肉豆蔻酰化位点的 Src 相关激酶）是 BRK 家族激酶（BFK）的成员，它代表了 Src 家族激酶的进化上保守的亲戚。 SFK）。已知酪氨酸激酶通过直接磷酸化底物蛋白和/或通过参与导致各种信号中间体的间接调节的信号串扰来调节许多细胞过程和途径。在之前的一项研究中，我们分析了 SRMS 的酪氨酸磷酸蛋白质组，并确定了该激酶的多个候选底物。SRMS 更广泛的细胞信号传导中间体是未知的。方法 为了揭示更广泛的 SRMS 调节的磷酸蛋白质组并鉴定 SRMS 调节的间接信号中间体，我们对表达野生型 SRMS 的细胞进行了无标记的全局磷酸蛋白质组学分析。使用计算数据库搜索和生物信息学分析，我们对数据集进行了表征。结果 我们的分析确定了从 140 个过度磷酸化肽中定位的 60 种过度磷酸化（磷酸丝氨酸/磷酸苏氨酸）蛋白。生物信息学分析确定了许多显着丰富的生物和细胞过程，其中发现 DNA 修复途径被上调，而凋亡途径被发现被下调。对源自上调磷酸位点的基序的分析确定酪蛋白激酶 2 α (CK2α) 是有助于 SRMS 依赖的信号中间体间接调节的主要潜在激酶之一。结论 总体而言，