The SH2-containing protein-tyrosine phosphatase SH-PTP2 is required upstream of MAP kinase for early Xenopus development.
SH-PTP2, the vertebrate homolog of Drosophila corkscrew, associates with several activated growth factor receptors, but its biological function is unknown. We assayed the effects of injection of wild-type and mutant SH-PTP2 RNAs on Xenopus embryogenesis. An internal phosphatase domain deletion (delta P) acts as a dominant negative mutant, causing severe posterior truncations. This phenotype is rescued by SH-PTP2, but not by the closely related SH-PTP1. In ectodermal explants, delta P blocks fibroblast growth factor (FGF)- and activin-mediated induction of mesoderm and FGF-induced mitogen-activated protein (MAP) kinase activation. Our results indicate that SH-PTP2 is required for early vertebrate development, acting as a positive component in FGF signaling downstream of the FGF receptor and upstream of MAP kinase.
Department of Microbiology and Molecular Genetics, Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02215.
T L
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Tang
R M
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Freeman
A M
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O'Reilly
B G
BG
Neel
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SY
Sokol
D028341:Activins; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D046508:Culture Techniques; D004475:Ectoderm / Q000187:drug effects / Q000502:physiology*; D004627:Embryonic Induction / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007265:Inhibins / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008648:Mesoderm / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000502:physiology; D014981:Xenopus
D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D028341:Activins; D007265:Inhibins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases