Non-receptor tyrosine kinases in mammalian neurogenesis.
Several members of the Src family of non-receptor tyrosine kinases are expressed at high levels in embryonic neural tissues as well as in adult brain. Relatively little has been known, however, about their roles in neural development. Attempts to clarify this by production of mutant mice have been unsuccessful because of gene redundancy. We earlier isolated a new cytoplasmic protein tyrosine kinase, Csk, and showed that it inactivates uniquely all members of non-receptor tyrosine kinases in vitro. Here, we have generated Csk-deficient mouse embryos and shown that Csk is indeed an indispensable negative regulator for all non-receptor tyrosine kinases in vivo, and that regulated activity of these kinases is essential for normal development of mice at the neural stage. The signaling pathway through Src-family kinases during neurulation is also discussed.
Aizawa
S
S
Laboratory of Molecular Oncology Tsukuba Life Science Center, Ibaraki, Japan.
Yagi
T
T
Furuta
Y
Y
Ikawa
Y
Y
Nada
S
S
Nakagawa
H
H
Okada
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D000081247:CSK Tyrosine-Protein Kinase; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005136:Eye Proteins; D005326:Fetal Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009420:Nervous System / Q000196:embryology*; D000072041:PAX3 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D012097:Repressor Proteins; D014157:Transcription Factors; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; D005136:Eye Proteins; D005326:Fetal Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000072041:PAX3 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C068686:Pax3 protein, mouse; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases