Zhu Shudong, Wang Hui, Ranjan Kamakshi, Zhang Dianzheng
School of Medicine, Nantong University, Nantong, China.
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, United States.
Front Cell Dev Biol. 2023 Jun 16;11:1206539. doi: 10.3389/fcell.2023.1206539. eCollection 2023.
The Src family kinases (SFK) plays an important role in multiple signal transduction pathways. Aberrant activation of SFKs leads to diseases such as cancer, blood disorders, and bone pathologies. By phosphorylating and inactivating SFKs, the C-terminal Src kinase (CSK) serves as the key negative regulator of SFKs. Similar to Src, CSK is composed of SH3, SH2, and a catalytic kinase domain. However, while the Src kinase domain is intrinsically active, the CSK kinase domain is intrinsically inactive. Multiple lines of evidence indicate that CSK is involved in various physiological processes including DNA repair, permeability of intestinal epithelial cells (IECs), synaptic activity, astrocyte-to-neuron communication, erythropoiesis, platelet homeostasis, mast cell activation, immune and inflammation responses. As a result, dysregulation of CSK may lead to many diseases with different underlying molecular mechanisms. Furthermore, recent findings suggest that in addition to the well-established CSK-SFK axis, novel CSK-related targets and modes of CSK regulation also exist. This review focuses on the recent progress in this field for an up-to-date understanding of CSK.
Src家族激酶（SFK）在多种信号转导途径中发挥重要作用。SFK的异常激活会导致癌症、血液疾病和骨骼疾病等病症。通过磷酸化并使SFK失活，C末端Src激酶（CSK）充当SFK的关键负调节因子。与Src相似，CSK由SH3、SH2和一个催化激酶结构域组成。然而，虽然Src激酶结构域具有内在活性，但CSK激酶结构域是内在无活性的。多项证据表明，CSK参与多种生理过程，包括DNA修复、肠上皮细胞（IEC）通透性、突触活动、星形胶质细胞与神经元的通信、红细胞生成、血小板稳态、肥大细胞激活、免疫和炎症反应。因此，CSK的失调可能导致许多具有不同潜在分子机制的疾病。此外，最近的研究结果表明，除了已确立的CSK-SFK轴外，还存在与CSK相关的新靶点和CSK调节模式。本综述重点关注该领域的最新进展，以便对CSK有最新的了解。
