Expression of mutated Nck SH2/SH3 adaptor respecifies mesodermal cell fate in Xenopus laevis development
AUTOR(ES)
Tanaka, Masamitsu
FONTE
The National Academy of Sciences of the USA
RESUMO
Nck is a widely expressed SH2/SH3 adaptor protein containing one SH2 and three SH3 domains. Although Nck is assumed to mediate the formation of protein-protein complexes during signaling, little is currently known about its specific function. We have constructed a series of Nck SH3 and SH2 domain mutants, expressed them in Xenopus laevis embryos, and monitored injected embryos for developmental abnormalities. This approach allows correlation of developmental phenotypes with the presence or absence of specific Nck protein-binding domains. We show that microinjection of RNA-encoding Nck with an inactivating mutation in the third SH3 domain (NckK229) into dorsal blastomeres of early embryos caused anterior truncation with high frequency, and membrane localization of both the first and second SH3 domains together was sufficient to induce this anterior-truncation phenotype. Molecular marker analysis of explants revealed that the expression of NckK229 ventralized dorsal mesoderm. Lineage tracing experiments demonstrated that the expression of Nck K229 in dorsal blastomeres affected the migratory properties of mesoderm cells in gastrulation and led to the adoption of a more posterior fate. These data suggest that protein(s) that bind the first and second SH3 domains of Nck can affect the response to signals that establish dorso-ventral patterning, and that protein(s) that bind the third SH3 domain antagonize the ventralizing effect of the first two SH3 domains.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=20750Documentos Relacionados
- Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila.
- The Murine Nck SH2/SH3 Adaptors Are Important for the Development of Mesoderm-Derived Embryonic Structures and for Regulating the Cellular Actin Network
- Differential inhibition of signaling pathways by dominant-negative SH2/SH3 adapter proteins.
- The SH2- and SH3-containing Nck protein transforms mammalian fibroblasts in the absence of elevated phosphotyrosine levels.
- Expression of GATA-binding proteins during embryonic development in Xenopus laevis.