Apoptosis regulation by the tyrosine-protein kinase CSK

Abstract

C-terminal Src kinase (CSK) is a cytosolic tyrosine-protein kinase with an important role in regulating critical cellular decisions, such as cellular apoptosis, survival, proliferation, cytoskeletal organization and many others. Current knowledge on the CSK mechanisms of action, regulation and functions is still at an early stage, most of CSK’s known actions and functions being mediated by the negative regulation of the SRC family of tyrosine kinases (SFKs) through phosphorylation. As SFKs play a vital role in apoptosis, cell proliferation and survival regulation, SFK inhibition by CSK has a pro-apoptotic effect, which is mediated by the inhibition of cellular signaling cascades controlled by SFKs, such as the MAPK/ERK, STAT3 and PI3K/AKT signaling pathways. Abnormal functioning of CSK and SFK activation can lead to diseases such as cancer, cardiovascular and neurological manifestations. This review describes apoptosis regulation by CSK, CSK inhibition of the SFKs and further explores the clinical relevance of CSK in important pathologies, such as cancer, autoimmune, autoinflammatory, neurologic diseases, hypertension and HIV/AIDS.

Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers

“…CSK is crucial in regulating cellular processes such as apoptosis, survival, and proliferation. Its pivotal role in cancer cell signaling earmarks CSK as a promising target for cancer therapy ( Fortner et al, 2022 ). Similarly, CTSF, known for its significant involvement in the progression of various cancers ( Wei et al, 2022 ), neurodegenerative diseases ( van der Zee et al, 2016 ), and skin aging ( Takaya et al, 2023 ), garners attention.…”

Prediction of Prognosis in Patients with Sepsis Based on Platelet-Related Genes

“…Furthermore, miR-155 can restore the immune function and alleviate heart dysfunction by downregulating the expression of ARRB2 in septic mice [34]. CSK is a tyrosine kinase, and abnormal CSK activity may be associated with many diseases, including cancer, autoimmune diseases, and autoinflammatory diseases [35]. Gupta et al [36] showed that heat shock protein 90 can prolong the survival of neutrophils in sepsis patients by preventing the degradation of CSK and Caspase-8 by proteasomes.…”

Regulation, targets and functions of CSK

“…Meanwhile, CBP is synergistically strengthened by CD59 (Cong et al, 2018). The detailed molecular mechanism in CSK-mediated T cell apoptosis is described in detail by Fortner et al, 2022. T cell effector function depends on TNF receptor associated factor 3 (TRAF3). Upon activation, TRAF3 forms a CD3/CD28containing complex that dissociates CSK and PTPN22 from Lck.…”