A New Family of Receptor Tyrosine Kinases with a Venus Flytrap Binding Domain in Insects and Other Invertebrates Activated by Aminoacids

Arnaud Ahier,Daniel J Donoghue,Colette Dissous,Philippe Rondard,Siluo Huang,Jacques Trolet,Nadège Gouignard,Monique Gauthier,Jean-Philippe Pin,Naji Khayath,Gordon Langsley

doi:10.1371/journal.pone.0005651

Abstract

BackgroundTyrosine kinase receptors (RTKs) comprise a large family of membrane receptors that regulate various cellular processes in cell biology of diverse organisms. We previously described an atypical RTK in the platyhelminth parasite Schistosoma mansoni, composed of an extracellular Venus flytrap module (VFT) linked through a single transmembrane domain to an intracellular tyrosine kinase domain similar to that of the insulin receptor.Methods and FindingsHere we show that this receptor is a member of a new family of RTKs found in invertebrates, and particularly in insects. Sixteen new members of this family, named Venus Kinase Receptor (VKR), were identified in many insects. Structural and phylogenetic studies performed on VFT and TK domains showed that VKR sequences formed monophyletic groups, the VFT group being close to that of GABAB receptors and the TK one being close to that of insulin receptors. We show that a recombinant VKR is able to autophosphorylate on tyrosine residues, and report that it can be activated by L-arginine. This is in agreement with the high degree of conservation of the alpha amino acid binding residues found in many amino acid binding VFTs. The presence of high levels of vkr transcripts in larval forms and in female gonads indicates a putative function of VKR in reproduction and/or development.ConclusionThe identification of RTKs specific for parasites and insect vectors raises new perspectives for the control of human parasitic and infectious diseases.

Highlights

Receptor tyrosine kinases (RTKs) are single-pass membrane proteins constituted of an extracellular ligand-binding domain and an intracellular kinase domain [1]
Identified in S. mansoni was exclusively present in this organism, or was common to other species, we searched for possible orthologs in other animal genomes
Whereas vkr genes were present in the genome of several dipteras, including seven drosophilidae, vkr was not found in the genome of any species belonging to the melanogaster group (Fig. 2)

Summary

Introduction

Receptor tyrosine kinases (RTKs) are single-pass membrane proteins constituted of an extracellular ligand-binding domain and an intracellular kinase domain [1]. A large number of RTKs have been identified and classified into 20 subfamilies that mostly differ by the structural organization of their ligand recognition domain. These include, for examples, the epidermal growth factor receptors (EGFRs or ErbBs), the fibroblast growth factor receptors (FGFRs), the insulin and the insulin-like growth factor receptors (IR and IGFR), the platelet-derived growth factor receptors (PDGFRs), the vascular endothelial growth factor receptors (VEGFRs) and the protooncogene receptor tyrosine kinase ROS [2]. Tyrosine kinase receptors (RTKs) comprise a large family of membrane receptors that regulate various cellular processes in cell biology of diverse organisms. We previously described an atypical RTK in the platyhelminth parasite Schistosoma mansoni, composed of an extracellular Venus flytrap module (VFT) linked through a single transmembrane domain to an intracellular tyrosine kinase domain similar to that of the insulin receptor

Methods

Results

Discussion

Conclusion