Regulation, targets and functions of CSK

Abstract

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.

Identification of oxidative phosphorylation-related genes in moyamoya disease by combining bulk RNA-sequencing analysis and machine learning

“…CSK is a negative regulator of Src family kinases (SFKs) recruited to the plasma membrane by binding to transmembrane or adapter proteins to suppress signaling via various surface receptors by phosphorylating and maintaining several inactive positive effectors, such as FYN or LCK ( D and CJB, 1999 ; Sun and Ayrapetov, 2023 ). It plays important roles in cell growth, migration, differentiation, and immune response ( Zhu et al, 2023 ). There were several studies about the CSK on endothelial cells.…”

Investigating the Protective Effects of a Citrus Flavonoid on the Retardation Morphogenesis of the Oligodendroglia-like Cell Line by Rnd2 Knockdown

“…It is thus thought that the Rnd2 and Prag1 signaling unit actually regulates the phosphorylation states of Fyn in FBD-102b cells. To explore whether Rnd2 and Prag1 actually mediate the activity of Fyn, we evaluated the phosphorylation levels of both the Fyn autophosphorylation site (Tyr-420) in the kinase activation loop and the C-terminal negative phosphorylating tyrosine (Tyr-531) using negative regulators such as Csk [39][40][41][42]. In Rnd2-knocked-down FBD-102b cells, the phosphorylation of Tyr-420 was decreased, whereas the phosphorylation of Tyr-531 was increased (Figure 9).…”

Table2.XLSX

“…CSK is a negative regulator of Src family kinases (SFKs) recruited to the plasma membrane by binding to transmembrane or adapter proteins to suppress signaling via various surface receptors by phosphorylating and maintaining several inactive positive effectors, such as FYN or LCK (D and CJB, 1999;Sun and Ayrapetov, 2023). It plays important roles in cell growth, migration, differentiation, and immune response (Zhu et al, 2023). There were several studies about the CSK on endothelial cells.…”