CSK, Active

CSK is a cytoplasmic tyrosine kinase that has been shown to downregulate the tyrosine kinase activity of the c-src oncoprotein through tyrosine phosphorylation of the c-src carboxy terminus (1). Cell transformation by src oncoprotein is caused by several oncogenic mechanisms, which interfere with the carboxy terminal phosphorylation. The CSK could therefore potentially function as an anti-oncogene. CSK is ubiquitously expressed in human tissues as 2 mRNA species of 2.6 and 3.4 kb, although in some tissues and cell lines, only the larger mRNA is detected (2). A yeast 2-hybrid system has been used to identify proteins associated with CSK. The Src homology-3 (SH3) domain of CSK associates with a proline-rich region of PEP, a protein-tyrosine phosphatase expressed in hemopoietic cells (2). This association is highly specific and it is speculated that PEP may be an effector and/or regulator of CSK in T cells and other hemopoietic cells. An in situ hybridization has been used to map the CSK gene to chromosome 15q23-q25 (3).