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 hematopoietic 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 TNP-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.
Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 4 Blackfan Cir, Boston, MA 02115, USA.
Byeong-Chel
BC
Lee
Shalom
S
Avraham
Akira
A
Imamoto
Hava Karsenty
HK
Avraham
D000818:Animals; D000941:Antigens / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology; D019070:Cell Lineage / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007107:Immune System / Q000166:cytology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015851:Interleukin-7 / Q000494:pharmacology; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism
D000941:Antigens; D015851:Interleukin-7; D007371:Interferon-gamma; C086603:Matk protein, mouse; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)