The venus kinase receptor (VKR) family: structure and evolution

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.

Venus Kinase Receptors Control Reproduction in the Platyhelminth Parasite Schistosoma mansoni

“…Moreover, as VKRs are also expressed in the gonads of disease-transmitting insects (like Anopheles vector of malaria or Aedes vector of filaria and viruses) [28], [29], and are probably involved in similar physiological processes of reproduction in these organisms, VKRs might also represent interesting drug targets for novel strategies to control other vector-borne infectious diseases besides schistosomiasis.…”

Phylogenetic evidence for the modular evolution of metazoan signalling pathways

“…A novel RTK family-venus kinase receptor (VKR)-was recently identified in N. vectensis as well as several bilaterian lineages but is absent from sponges and Hydra. A search of the M. leidyi genome for the diagnostic VFT domain of VKR-related proteins failed to find any significant matches in this ctenophore, suggesting VKRs also evolved after ctenophores and sponges diverged from the cnidarian/bilaterian ancestor [126]. Also absent from ctenophores and sponges is the FGFR family of RTKs [128], which is known to have many important roles governing the development of cell and tissue identity in Cnidarians and Bilaterians.…”

A novel bacterial l‐arginine sensor controlling c‐di‐GMP levels in Pseudomonas aeruginosa

“…In general, PBPs trap nutrients for their internalization into bacteria by ABC transporters; they are commonly in the same operon of the permease counterpart . Nevertheless, the PBP‐fold and specificity is conserved also when fused to diverse sensory/transduction systems, not necessarily linked to the import event (ie, the so‐called “sensor‐PBPs”), conserved both in prokaryotes and in eukaryotes …”

“…15 Nevertheless, the PBP-fold and specificity is conserved also when fused to diverse sensory/transduction systems, not necessarily linked to the import event (ie, the so-called "sensor-PBPs"), conserved both in prokaryotes and in eukaryotes. 14,[16][17][18] Regardless of the function, ligand binding triggers closure of the VFT by bringing its two domains together, like a Venus flytrap of the carnivorous plant Dionaea muscipula, from which its name derives.…”