Specific and redundant roles of Src and Fyn in organizing the cytoskeleton

• Published in: Nature (London) 1995-07, Vol.376 (6537), p.267-271
• Main Authors: Thomas, Sheila M, Soriano, Philippe, Imamoto, Akira
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biochemical analysis; Biochemistry; Biological and medical sciences; Cell Adhesion Molecules - physiology; Cell Line; Classical genetics, quantitative genetics, hybrids; Cytoskeleton - physiology; DNA Primers; Embryonic and Fetal Development - genetics; Embryonic and Fetal Development - physiology; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Humanities and Social Sciences; letter; Mice; Molecular Sequence Data; multidisciplinary; Mutagenesis; Mutation; Phenotype; Phosphorylation; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - physiology; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-fyn; Rodents; Science; Science (multidisciplinary); src-Family Kinases; Tyrosine - metabolism; Vertebrata
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/376267a0

MOUSE embryos lacking Csk, a negative regulator of Src family kinases, exhibit defects in neurulation and die at mid-gestation 1,2 . To determine the role of activated Src family kinases in the csk - phenotype, we have introduced mutations in the src and fyn genes 3,4 into the csk - mutant background. Genetic analysis reveals that src , but not fyn , is partly epistatic to the csk gene. Biochemical analysis indicates that several cytoskeletal proteins are hyperphosphorylated on tyrosine residues in csk - cells. Regulation of cortactin and tensin hyperphosphorylation is Src-dependent, whereas focal adhesion kinase and paxillin hyperphosphorylation is partly dependent on both Src and Fyn. Furthermore, the src- mutation can restore the normal distribution of cortactin and partly correct filamentous actin organization in csk - cells. Thus, Src family kinases have both specific and overlapping functions in regulation of the cytoskeleton. The disturbance of these functions may be a molecular basis for the phenotype exhibited by csk - mutants.