Conservation and Early Expression of Zebrafish Tyrosine Kinases Support the Utility of Zebrafish as a Model for Tyrosine Kinase Biology

Abstract

Tyrosine kinases have significant roles in cell growth, apoptosis, development, and disease. To explore the use of zebrafish as a vertebrate model for tyrosine kinase signaling and to better understand their roles, we have identified all of the tyrosine kinases encoded in the zebrafish genome and quantified RNA expression of selected tyrosine kinases during early development. Using profile hidden Markov model analysis, we identified 122 zebrafish tyrosine kinase genes and proposed unambiguous gene names where needed. We found them to be organized into 39 nonreceptor and 83 receptor type, and 30 families consistent with human tyrosine kinase family assignments. We found five human tyrosine kinase genes (epha1, bmx, fgr, srm, and insrr) with no identifiable zebrafish ortholog, and one zebrafish gene (yrk) with no identifiable human ortholog. We also found that receptor tyrosine kinase genes were duplicated more often than nonreceptor tyrosine kinase genes in zebrafish. We profiled expression levels of 30 tyrosine kinases representing all families using direct digital detection at different stages during the first 24 hours of development. The profiling experiments clearly indicate regulated expression of tyrosine kinases in the zebrafish, suggesting their role during early embryonic development. In summary, our study has resulted in the first comprehensive description of the zebrafish tyrosine kinome.

Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates

“…Among the Teleleostei, Ostariophysii have experienced some distinct losses compared with the Neotelostei (Percomorpha and Gadiformes). EphA6b , ephB4b , and pdgfrBb are present neither in zebrafish ( Challa and Chatti 2013 ) nor in cavefish, extending these features to be common for the Ostariophysi lineage. EphA4lb , tek , and ros1 are missing in Neoteleostei.…”

“…With the additional 3R-WGD, RTKs rose up to a total number of 84 RTK genes in teleost fish, with at most 81 present in each of the studied species. It has been noted that the human EphA1 and Insrr have no counterpart in zebrafish ( Challa and Chatti 2013 ). Here, we extend this finding and show that these gene losses characterize all fish genomes available to date, including teleosts and the more basal lineages.…”

Embryo Microinjection of Selenomethionine Reduces Hatchability and Modifies Oxidant Responsive Gene Expression in Zebrafish

“…There is a balance between the activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) in cells that plays a pivotal role in cell signaling and animal development 42 43 44 . Oxidative stress and exposure to chemicals including SeMet have been demonstrated to inhibit transcript abundance and/or activity of protein tyrosine phosphatase 1B both in vitro and in vivo 25 42 45 46 .…”

Paralog-Specific Patterns of Structural Disorder and Phosphorylation in the Vertebrate SH3–SH2–Tyrosine Kinase Protein Family

“…While human and mouse kinomes have been broadly studied, little is known about fish kinomes which are also relevant to a broad range of experiments in health and disease. For instance, Zebrafish ( Danio rerio ) is a popular model organism of human cancers, TK signaling, and pharmaceutical development ( Challa and Chatti 2013 ; Gibert et al 2013 ). Preliminary drafts of the Zebrafish kinome ( Challa and Chatti 2013 ; Rakshambikai et al 2014 ) show that a large number of recent kinase gene duplicates are retained, but lack a human counterpart ( Wlodarchak et al 2015 ).…”