Regulation of Laloo by the Xenopus C-terminal Src kinase (Xcsk) during early vertebrate development.
Mesoderm formation in the frog, Xenopus laevis, is dependent on the activity of one or more members of the Src family kinases; the molecular interactions underlying this requirement are not well understood. The C-terminal Src Kinase (Csk) is a potent inhibitor of Src activity, and is required for normal mammalian development; here we report the characterization of Xenopus Csk (Xcsk). Xcsk is widely expressed during early development, physically interacts with the Src kinase Laloo, and inhibits the generation of mesoderm by the Src kinases. Xcsk activity requires a functional kinase domain; furthermore, a kinase-inactive Xcsk mutant potently synergizes with Laloo during early vertebrate development, suggesting a fundamental role for the Src kinase-Csk regulatory circuit during mesoderm induction, in vivo.
Song
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Department of Pharmacology, Mount Sinai School of Medicine, New York, NY, USA.
Cohler
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Weinstein
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D000595:Amino Acid Sequence; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008648:Mesoderm / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014981:Xenopus; D029867:Xenopus Proteins; D019061:src-Family Kinases / Q000378:metabolism*
C114358:HCK protein, Xenopus; D011518:Proto-Oncogene Proteins; D029867:Xenopus Proteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C494963:Fyn protein, Xenopus; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases