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]
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.