ZFIN ID: ZDB-PUB-000309-18
Pleiotropic effects of zebrafish protein-tyrosine phosphatase-1B on early embryonic development
van der Sar, A.M., de Fockert, J., Betist, M., Zivkovic, D., and den Hertog, J.
Date: 1999
Source: The International journal of developmental biology   43(8): 785-794 (Journal)
Registered Authors: de Fockert, Jaco, den Hertog, Jeroen, Jongejan-Zivkovic, Dana
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • DNA Primers/genetics
  • Endoplasmic Reticulum/enzymology
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • In Situ Hybridization
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phenotype
  • Protein Tyrosine Phosphatases/genetics
  • Protein Tyrosine Phosphatases/metabolism*
  • Sequence Homology, Amino Acid
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
PubMed: 10707902
ABSTRACT
Protein tyrosine phosphorylation is an important mechanism of eukaryotic cell signalling which is regulated by protein-tyrosine kinases and protein-tyrosine phosphatases. Here we report the molecular cloning of the first zebrafish protein-tyrosine phosphatase, zf-PTP-1B, the homologue of human PTP-1B. Zf-PTP-1B was catalytically active and localised to the endoplasmic reticulum, like human PTP-1B. Zf-PTP-1B was maternally expressed in zebrafish embryos, and low ubiquitous expression was detected up to day 7 of development. Microinjection of zf-PTP-1B RNA induced pleiotropic, but reproducible developmental defects. Evaluation of the live embryos at 24 h post fertilisation indicated that zf-PTP-1B induced defects in somite formation. The phenotype was dependent on protein-tyrosine phosphatase activity of zf-PTP-1B, since embryos injected with catalytically inactive zf-PTP-1B-C213S developed normally. Co-injection of wild type and inactive zf-PTP-1B led to a rescue of the zf-PTP-1B-induced phenotype, suggesting that zf-PTP-1B-C213S had dominant negative activity. The zf-PTP-1B-induced phenotype suggests that proper tyrosine phosphorylation of key proteins is essential for early development, most notably somitogenesis.
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