![]() ![]() The cerebral cortex is responsible for higher cognitive functions. 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. Abnormal functioning of CSK and SFK activation can lead to diseases such as cancer, cardiovascular and neurological manifestations. 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. 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. Symbols listed in the framed box indicate representative domains.Ĭ-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. Abbreviations: BAR, Bin/Amphiphysin/Rvs CRIB, CDC42-Rac interactive binding F-BAR, Fes/CIP4 homology-BAR FX, F-BAR extension HR1, Protein kinase C-related kinase homology region 1 I-BAR, Inverse BAR N-BAR, N-terminal amphipathic helix BAR NPF, Asparagine proline phenylalanine RhoGAP, Rho GTPase-activating protein SH2, Src homology-2 SH3, Src homology-3 WH2, WASP homology 2 Tyr-kinase, Tyrosine kinase μHD, μ-homology domain. Crystal structure (a red monomer and a green monomer forming a dimer) is generated by using Protein Data Bank (PDB, ). Domain information is based on previous publications 1, 3, 4, 7, 8. F-BAR, N-BAR, and I-BAR proteins bind to cell membrane and lead to different forms of curvature changes. (D) Membrane curvature forms caused by BAR domain proteins. F-BAR family has nine subfamilies determined by the specific domain combination. Bar domain proteins can form homodimer which binds to cell membrane leading to membrane curvature. BAR domain superfamily consists of three families based on distinct domain structures of F-BAR, N-BAR, and I-BAR. ![]() F-BAR, N-BAR and I-BAR family domain structure and membrane curvature models. ![]()
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