Impaired development of CD4+ CD8+ thymoyctes by csk-'knock-in' into fyn locus.
p59fyn is one of the Src-family kinases thought to play an important role in signaling through T cell receptor. However, Fyn deficiency has caused no overt defects in vivo on T cell development, nor has it caused any changes in the phosphorylation status of molecules such as ZAP-70 which have been proposed as p59fyn substrates. This could be explained as being due to compensation of Fyn deficiency by other Src-family kinases. Here, we have 'knocked-in' the csk gene, a negative regulator of Src-family kinases, into fyn locus to challenge the problem of redundant functions among Src-family kinases. The csk-'knock-in' mice displayed atrophy of the thymic cortex and impaired development of CD4+ CD8+ thymocytes. This was concomitant with decrease in tyrosine phosphorylation of ZAP-70 and p120cbl.
Kanazawa
S
S
Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Japan.
Ilic
D
D
Hashiyama
M
M
Okada
M
M
Noumura
T
T
Aizawa
S
S
Suda
T
T
D000818:Animals; D001483:Base Sequence; D000081247:CSK Tyrosine-Protein Kinase; D002454:Cell Differentiation; D018390:Gene Targeting; D005813:Genes, Synthetic; D016391:Genes, src; D006410:Hematopoiesis / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D016254:Mutagenesis, Insertional; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050721:Proto-Oncogene Proteins c-cbl; D051076:Proto-Oncogene Proteins c-fyn; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D013950:Thymus Gland / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases; D051746:ZAP-70 Protein-Tyrosine Kinase; D019061:src-Family Kinases / Q000235:genetics*
D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D019061:src-Family Kinases; C493849:Cbl protein, mouse