Identification of the nonreceptor tyrosine kinase MATK/CHK as an essential regulator of immune cells using Matk/CHK-deficient mice

Matk/CHK knockout mice were reported to show no apparent phenotypic abnormalities. This was thought to be due to the homologous kinase Csk that compensates for Matk/CHK. Here, we present the first evidence that the nonreceptor tyrosine kinase, Matk/CHK, is an important modulator of immune cell signaling. We found that the frequency of primitive hematopoletic cells, the side population c- kit+ Lin- Sca(-1+) (SPKLS) cells, in Matk/ CHK-/- mice was increased 2.2-fold compared with the control mice. Moreover, Matk/CHK deficiency led to significantly higher pre-B cell colony formation following IL-7 stimulation. Interestingly, when mice received the in vivo antigen challenge of TINP-ovalbumin followed by restimulation, the Matk/CHK-/- lymph node and spleen cells produced significantly lower IFN-gamma levels compared with the respective wild-type cells. Our study indicates that Matk/CHK is not functionally redundant with Csk, and that this tyrosine kinase plays an important role as a regulator of immunologic responses.