Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2

EMBO J. 1997 May 1;16(9):2352-64. doi: 10.1093/emboj/16.9.2352.

Abstract

Shp-1, Shp-2 and corkscrew comprise a small family of cytoplasmic tyrosine phosphatases that possess two tandem SH2 domains. To investigate the biological functions of Shp-2, a targeted mutation has been introduced into the murine Shp-2 gene, which results in an internal deletion of residues 46-110 in the N-terminal SH2 domain. Shp-2 is required for embryonic development, as mice homozygous for the mutant allele die in utero at mid-gestation. The Shp-2 mutant embryos fail to gastrulate properly as evidenced by defects in the node, notochord and posterior elongation. Biochemical analysis of mutant cells indicates that Shp-2 can function as either a positive or negative regulator of MAP kinase activation, depending on the specific receptor pathway stimulated. In particular, Shp-2 is required for full and sustained activation of the MAP kinase pathway following stimulation with fibroblast growth factor (FGF), raising the possibility that the phenotype of Shp-2 mutant embryos results from a defect in FGF-receptor signalling. Thus, Shp-2 modulates tyrosine kinase signalling in vivo and is crucial for gastrulation during mammalian development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Endothelium, Vascular / embryology
  • Endothelium, Vascular / enzymology
  • Enzyme Activation / genetics
  • Fibroblast Growth Factors / pharmacology
  • Gastrula / enzymology
  • Genes, Lethal
  • Intracellular Signaling Peptides and Proteins
  • Mesoderm / enzymology*
  • Mice
  • Mutation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • Signal Transduction / genetics
  • src Homology Domains*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Fibroblast Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, mouse
  • Ptpn6 protein, mouse
  • SH2 Domain-Containing Protein Tyrosine Phosphatases