Tyrosine-protein kinase CSK

CSK
Available structures PDB Ortholog search: H3BU69 PDBe H3BU69 RCSB List of PDB id codes 1BYG, 1CSK, 3D7T, 3D7U, 3EAC, 3EAZ
Identifiers
Aliases	CSK, Src, c-src tyrosine kinase, CSK/Src, non-receptor tyrosine kinase, C-terminal Src kinase
External IDs	OMIM: 190090, 124095; MGI: 88537; HomoloGene: 55818; GeneCards: CSK; OMA:CSK - orthologs
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q24.1 Start 74,782,057 bp[1] End 74,803,198 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 B|9 31.18 cM Start 57,533,929 bp[2] End 57,560,914 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte monocyte spleen blood lymph node appendix mucosa of transverse colon tonsil bone marrow cells stromal cell of endometrium Top expressed in granulocyte mesenteric lymph nodes thymus spleen neural layer of retina lip ventricular zone blood yolk sac gastrula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein kinase activity protein kinase A catalytic subunit binding non-membrane spanning protein tyrosine kinase activity metal ion binding protein C-terminus binding protein binding identical protein binding protein tyrosine kinase activity protein phosphatase binding proline-rich region binding signaling receptor binding ATP binding kinase activity Cellular component cytoplasm cytosol membrane cell-cell junction extrinsic component of cytoplasmic side of plasma membrane plasma membrane membrane raft extracellular exosome Biological process cell differentiation adaptive immune response positive regulation of MAP kinase activity epidermal growth factor receptor signaling pathway negative regulation of phagocytosis phosphorylation transmembrane receptor protein tyrosine kinase signaling pathway negative regulation of low-density lipoprotein particle clearance immune system process negative regulation of interleukin-6 production T cell costimulation oligodendrocyte differentiation negative regulation of Golgi to plasma membrane protein transport regulation of Fc receptor mediated stimulatory signaling pathway regulation of cytokine production protein phosphorylation brain development cellular response to peptide hormone stimulus regulation of cell population proliferation peptidyl-tyrosine autophosphorylation negative regulation of ERK1 and ERK2 cascade protein autophosphorylation innate immune response adherens junction organization T cell receptor signaling pathway negative regulation of cell population proliferation negative regulation of bone resorption negative regulation of kinase activity central nervous system development peptidyl-tyrosine phosphorylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1445 12988 Ensembl ENSG00000103653 ENSMUSG00000032312 UniProt P41240 P41241 RefSeq (mRNA) NM_001127190 NM_004383 NM_001354988 NM_007783 NM_001304761 RefSeq (protein) NP_001120662 NP_004374 NP_001341917 NP_001291690 NP_031809 Location (UCSC) Chr 15: 74.78 – 74.8 Mb Chr 9: 57.53 – 57.56 Mb PubMed search [3] [4]
Wikidata
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Tyrosine-protein kinase CSK also known as C-terminal Src kinase is an enzyme that, in humans, is encoded by the CSK gene.^[5] This enzyme phosphorylates tyrosine residues located in the C-terminal end of Src-family kinases (SFKs) including SRC, HCK, FYN, LCK, LYN and YES1.^[6][7]

Function

This Non-receptor tyrosine-protein kinase plays an important role in the regulation of cell growth, differentiation, migration and immune response. CSK acts by suppressing the activity of the Src family of protein kinases by phosphorylation of Src family members at a conserved C-terminal tail site in Src.^{[8][9][10][11]} Upon phosphorylation by other kinases, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is then recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane and ultimately suppresses signaling through various surface receptors, including T-cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several effector molecules.^[6][7]

Role in development and regulation

Tyrosine-protein kinase CSK is involved in the following developmental, metabolic, and signal transduction cascades:

Adherens junction organization, blood coagulation, brain development, cell differentiation, cell migration, cellular response to peptide hormone stimulus, central nervous system development, epidermal growth factor receptor signaling pathway, innate immune response, epithelium morphogenesis, regulation of bone resorption, negative regulation of cell proliferation, negative regulation of ERK1 and ERK2 cascade, negative regulation of Golgi to plasma membrane protein transport, negative regulation of interleukin-6 production, negative regulation of kinase activity, negative regulation of low-density lipoprotein particle clearance, negative regulation of phagocytosis, dendrocyte differentiation, peptidyl-tyrosine autophosphorylation, platelet activation, positive regulation of MAP kinase activity, regulation of cell proliferation, regulation of cytokine production, regulation of Fc receptor mediated stimulatory signaling pathway, T cell costimulation, T cell receptor signaling pathway.^[12]

Expression and subcellular location

CSK is expressed in the lungs and macrophages as well as several other tissues.^[13] Tyrosine-Kinase CSK is mainly present in the cytoplasm, but also found in lipid rafts making cell-cell junction.^[12]

Mutations

• Y184F – Abolishes phosphorylation.^[14]
• Y304F – Decreases activity by two-thirds and alters conformation.^[14]
• S364A – Strong decrease of phosphorylation by PRKACA (the catalytic subunit of protein kinase A).^[15]

Clinical significance

Csk's interaction with a phosphatase ("Lyp", gene product of PTPN22) is possibly associated with the increased autoimmune diseases associated with PTPN22 mutations.^[16]

References

External links

• CSK tyrosine-protein kinase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)