Abstract
BackgroundReceptor tyrosine kinases (RTK) form a family of transmembrane proteins widely conserved in Metazoa, with key functions in cell-to-cell communication and control of multiple cellular processes. A new family of RTK named Venus Kinase Receptor (VKR) has been described in invertebrates. The VKR receptor possesses a Venus Fly Trap (VFT) extracellular module, a bilobate structure that binds small ligands to induce receptor kinase activity. VKR was shown to be highly expressed in the larval stages and gonads of several invertebrates, suggesting that it could have functions in development and/or reproduction.ResultsAnalysis of recent genomic data has allowed us to extend the presence of VKR to five bilaterian phyla (Platyhelminthes, Arthropoda, Annelida, Mollusca, Echinodermata) as well as to the Cnidaria phylum. The presence of NveVKR in the early-branching metazoan Nematostella vectensis suggested that VKR arose before the bilaterian radiation. Phylogenetic and gene structure analyses showed that the 40 receptors identified in 36 animal species grouped monophyletically, and likely evolved from a common ancestor. Multiple alignments of tyrosine kinase (TK) and VFT domains indicated their important level of conservation in all VKRs identified up to date. We showed that VKRs had inducible activity upon binding of extracellular amino-acids and molecular modeling of the VFT domain confirmed the structure of the conserved amino-acid binding site.ConclusionsThis study highlights the presence of VKR in a large number of invertebrates, including primitive metazoans like cnidarians, but also its absence from nematodes and chordates. This little-known RTK family deserves to be further explored in order to determine its evolutionary origin, its possible interest for the emergence and specialization of Metazoa, and to understand its function in invertebrate development and/or reproductive biology.
Highlights
Receptor tyrosine kinases (RTK) form a family of transmembrane proteins widely conserved in Metazoa, with key functions in cell-to-cell communication and control of multiple cellular processes
No unequivocal Venus Kinase Receptor (VKR) sequence could be found in the genome of the planarian Schmidtea mediterranea, but a sequence encoding a polypeptide composed of a TK domain and a truncated Venus Fly Trap (VFT) module (GenBank: AAWT01078636.1) was identified, suggesting that a vkr gene might still exist in Turbellaria
A maximum likelihood phylogenetic tree was generated under the JTT+I+G model with the support of three outgroups composed respectively of insulin, RTK-like orphan (ROR) and epidermal growth factor (EGF) receptors of invertebrates (Figure 1)
Summary
Receptor tyrosine kinases (RTK) form a family of transmembrane proteins widely conserved in Metazoa, with key functions in cell-to-cell communication and control of multiple cellular processes. RTKs have essential multicellular-specific functions, including cell-to-cell communications, control of cell proliferation and differentiation [1]. They have been found in all metazoan genomes, from the marine sponge Geodia cydonium to humans [2,3]. VKR kinases can be activated following the binding of amino-acids to the extracellular VFT domain [12,14], and this opens interesting perspectives on a novel mechanism for RTK activation as well as on possible specific and new functions of these receptors in cellular signalling
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