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

Tracy M. Saxton, Mark Henkemeyer, Stéphan Gasca, Randy Shen, Derrick J. Rossi, Fouad Shalaby, Gen Sheng Feng, Tony Pawson

Research output: Contribution to journalArticle

370 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2352-2364
Number of pages13
JournalEMBO Journal
Volume16
Issue number9
DOIs
StatePublished - May 1 1997

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Non-Receptor Type 11 Protein Tyrosine Phosphatase
src Homology Domains
Mesoderm
Phosphotransferases
Embryonic Structures
Chemical activation
TYK2 Kinase
Notochord
Fibroblast Growth Factor Receptors
Gastrulation
Defects
Fibroblast Growth Factors
Phosphoric Monoester Hydrolases
Embryonic Development
Tyrosine
Elongation
Genes
Alleles
Phenotype
Pregnancy

Keywords

  • Gastrulation
  • Gene targeting
  • MAP kinase
  • Shp-2
  • Tyrosine phosphatase

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Saxton, T. M., Henkemeyer, M., Gasca, S., Shen, R., Rossi, D. J., Shalaby, F., ... Pawson, T. (1997). Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2. EMBO Journal, 16(9), 2352-2364. https://doi.org/10.1093/emboj/16.9.2352

Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2. / Saxton, Tracy M.; Henkemeyer, Mark; Gasca, Stéphan; Shen, Randy; Rossi, Derrick J.; Shalaby, Fouad; Feng, Gen Sheng; Pawson, Tony.

In: EMBO Journal, Vol. 16, No. 9, 01.05.1997, p. 2352-2364.

Research output: Contribution to journalArticle

Saxton, TM, Henkemeyer, M, Gasca, S, Shen, R, Rossi, DJ, Shalaby, F, Feng, GS & Pawson, T 1997, 'Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2', EMBO Journal, vol. 16, no. 9, pp. 2352-2364. https://doi.org/10.1093/emboj/16.9.2352
Saxton, Tracy M. ; Henkemeyer, Mark ; Gasca, Stéphan ; Shen, Randy ; Rossi, Derrick J. ; Shalaby, Fouad ; Feng, Gen Sheng ; Pawson, Tony. / Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2. In: EMBO Journal. 1997 ; Vol. 16, No. 9. pp. 2352-2364.
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