Department of Molecular Genetics, Institute of Biology, University of Hohenheim, 70599 Stuttgart, Germany.
Institute of Biology, University of Hohenheim, 70599 Stuttgart, Germany.
Cells. 2024 Mar 26;13(7):576. doi: 10.3390/cells13070576.
Blood cells in serve primarily innate immune responses. Various stressors influence blood cell homeostasis regarding both numbers and the proportion of blood cell types. The principle molecular mechanisms governing hematopoiesis are conserved amongst species and involve major signaling pathways like Notch, Toll, JNK, JAK/Stat or RTK. Albeit signaling pathways generally rely on the activity of protein kinases, their specific contribution to hematopoiesis remains understudied. Here, we assess the role of Serine/Threonine kinases with the potential to phosphorylate the transcription factor Su(H) in crystal cell homeostasis. Su(H) is central to Notch signal transduction, and its inhibition by phosphorylation impedes crystal cell formation. Overall, nearly twenty percent of all Serine/Threonine kinases were studied in two assays, global and hemocyte-specific overexpression and downregulation, respectively. Unexpectedly, the majority of kinases influenced crystal cell numbers, albeit only a few were related to hematopoiesis so far. Four kinases appeared essential for crystal cell formation, whereas most kinases restrained crystal cell development. This group comprises all kinase classes, indicative of the complex regulatory network underlying blood cell homeostasis. The rather indiscriminative response we observed opens the possibility that blood cells measure their overall phospho-status as a proxy for stress-signals, and activate an adaptive immune response accordingly.
血细胞在先天免疫反应中起主要作用。各种应激源影响血细胞的数量和比例，从而影响血细胞的内环境稳定。调节造血的主要分子机制在物种间是保守的，涉及 Notch、Toll、JNK、JAK/Stat 或 RTK 等主要信号通路。尽管信号通路通常依赖于蛋白激酶的活性，但它们对造血的具体贡献仍研究不足。在这里，我们评估了丝氨酸/苏氨酸激酶在晶体细胞内环境稳定中的作用，这些激酶有可能磷酸化转录因子 Su(H)。Su(H)是 Notch 信号转导的核心，其磷酸化抑制晶体细胞的形成。总的来说，在两个实验中研究了将近 20%的所有丝氨酸/苏氨酸激酶，分别是全局和血淋巴细胞特异性过表达和下调。出乎意料的是，大多数激酶影响晶体细胞的数量，但迄今为止只有少数与造血有关。有 4 种激酶对晶体细胞的形成是必需的，而大多数激酶则限制晶体细胞的发育。这组激酶包括所有的激酶类，表明血细胞内环境稳定的背后存在着复杂的调控网络。我们观察到的这种相当无差别地反应，使得血细胞将其整体磷酸化状态作为应激信号的替代指标，并相应地激活适应性免疫反应成为可能。
