Pleiotropic effects of zebrafish Protein-Tyrosine Phosphatase-1B on early embryonic development

Protein tyrosine phosphorylation is an important mechanism of eukaryotic ce ll signalling which is regulated by protein-tyrosine kinases and protein-ty rosine phosphatases. Here we report the molecular cloning of the first zebr afish protein-tyrosine phosphatase, zf-PTP-1B, the homologue of human PTP-1 B. ZC-PTP-1B was catalytically active and localised to the endoplasmic reti culum, like human PTP-1B. Zf-PTP-1B was maternally expressed in zebrafish e mbryos, and low ubiquitous expression was detected up to day 7 of developme nt. Microinjection of zf-PTP-1B RNA induced pleiotropic, but reproducible d evelopmental defects. Evaluation of the live embryos at 24 h post fertilisa tion indicated that zf-PTP-1B induced defects in somite formation. The phen otype was dependent on protein-tyrosine phosphatase activity of zf-PTP-1B, since embryos injected with catalytically inactive zf-PTP-1B-C213S develope d norm ally. Go-injection of wild type a nd inactive zf-PTP-1B led to a res cue 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 deve lopment, most notably somitogenesis.