The molecular basis of Src kinase specificity during vertebrate mesoderm formation.

The Journal of Biological Chemistry
J HamaD C Weinstein

Abstract

Members of the Src family of non-receptor tyrosine kinases play a critical role in mesoderm formation in the frog, Xenopus laevis, acting as required mediators downstream of the fibroblast growth factor receptor. At least four members of this gene family, Src, Fyn, Yes, and Laloo, are expressed during early embryonic development. Ectopic expression of Laloo and Fyn, but not Src, induce mesoderm in ectodermal explants, indicating that these factors are non-redundant during early vertebrate development. Here we investigate the basis for the differential activity of the Src and Laloo kinases during mesoderm formation. We demonstrate that although both Src and Laloo physically interact with the substrate protein SNT-1/FRS2alpha only Laloo phosphorylates SNT-1, an event previously shown to be required for the activity of the latter and for mesoderm induction in vivo. We show that Src is enzymatically capable of stimulating mesoderm formation, as an activated Src construct both phosphorylates SNT-1 and induces mesoderm in explant cultures. However, a chimeric Laloo construct containing a Src C-terminal tail is inactive, suggesting that the early embryo contains a specific Laloo-activating, or Src-inactivating, factor. Finally, throug...Continue Reading

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Citations

Apr 5, 2008·PLoS Computational Biology·Ignacio E SánchezLuis Serrano
Jul 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Tomomi HaremakiDaniel C Weinstein
Sep 5, 2012·Developmental Biology·Tomomi Haremaki, Daniel C Weinstein
Dec 2, 2004·Developmental Biology·Wen-Bin TsaiWilliam H Kinsey
Aug 23, 2005·Developmental Biology·Dipika SharmaWilliam H Kinsey
Dec 4, 2003·Developmental Biology·M Marcela Cardenas, Luis M Salgado
May 30, 2020·BMC Molecular and Cell Biology·Shoshana ReichDaniel C Weinstein
Jun 28, 2015·Development·Alessia DeglincertiAli H Brivanlou

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