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]
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]
Csk's interaction with a phosphatase ("Lyp", gene product of PTPN22) is possibly associated with the increased autoimmune diseases associated with PTPN22 mutations.[16]
^ abSun G, Budde RJ (Sep 1997). "Expression, purification, and initial characterization of human Yes protein tyrosine kinase from a bacterial expression system". Archives of Biochemistry and Biophysics. 345 (1): 135–42. doi:10.1006/abbi.1997.0236. PMID9281320.
^Nada S, Okada M, MacAuley A, Cooper JA, Nakagawa H (May 1991). "Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src". Nature. 351 (6321): 69–72. Bibcode:1991Natur.351...69N. doi:10.1038/351069a0. PMID1709258. S2CID4363527.
^Nada S, Yagi T, Takeda H, Tokunaga T, Nakagawa H, Ikawa Y, Okada M, Aizawa S (Jun 1993). "Constitutive activation of Src family kinases in mouse embryos that lack Csk". Cell. 73 (6): 1125–35. doi:10.1016/0092-8674(93)90642-4. PMID8513497. S2CID37988394.
^Chong YP, Mulhern TD, Cheng HC (Sep 2005). "C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK)--endogenous negative regulators of Src-family protein kinases". Growth Factors. 23 (3): 233–44. doi:10.1080/08977190500178877. PMID16243715. S2CID38227036.
^ abUniversal protein resource accession number P41240 for "Tyrosine-protein kinase CSK" at UniProt.
^Bräuninger A, Holtrich U, Strebhardt K, Rübsamen-Waigmann H (Jan 1992). "Isolation and characterization of a human gene that encodes a new subclass of protein tyrosine kinases". Gene. 110 (2): 205–11. doi:10.1016/0378-1119(92)90649-a. PMID1371489.