Regulation of Src family kinases in the developing rat brain: correlation with their regulator kinase, Csk.
We have so far suggested that the functions of Src family protein-tyrosine kinases are under the control of their regulator kinase, Csk. To evaluate the role of Csk-mediated regulation in neural tissues, we examined the correlation between the activities of Src family kinases and the expression level of Csk during development of the rat brain. Csk was expressed at high levels in the developing embryonic brain and then rapidly decreased as the brain matured. Consistent with the decrease in the Csk level, the kinase activity of a member of the Src family, Fyn, was greatly enhanced, but that of Src was not correlated inversely with the level of Csk expression. Src exhibited elevated activity in the developing brain, in which a neuronal form of Src (N-Src) is expressed as the dominant form of Src. Although N-Src was readily down-regulated by Csk when coexpressed in yeast, it showed much higher specific activity than c-Src, even in the repressed form. These findings suggest that neural tissues acquire high activities of Src family kinases, which might be important for differentiation and development of the nervous system, through induction of the active form of Src (N-Src) and down-regulation of their suppresser, Csk.
Inomata
M
M
Division of Protein Metabolism, Osaka University.
Takayama
Y
Y
Kiyama
H
H
Nada
S
S
Okada
M
M
Nakagawa
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D000081247:CSK Tyrosine-Protein Kinase; D015536:Down-Regulation / Q000502:physiology*; D015151:Immunoblotting; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012441:Saccharomyces cerevisiae; D019061:src-Family Kinases
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases