An unusual receptor tyrosine kinase of Schistosoma mansoni contains a Venus Flytrap module.
Previous studies have suggested that successful development of the parasitic helminth Schistosoma mansoni must be dependent on an adaptative molecular dialogue with its hosts and on the existence of receptors for growth factors and hormones. Attempts to identify a homolog of the insulin receptor (IR) have led us to characterize a new receptor tyrosine kinase (RTK) molecule in S. mansoni. SmRTK-1 is an integral membrane protein with a single membrane-spanning sequence separating an extracellular ligand-binding domain and a cytoplasmic TK domain. Structural and phylogenetic analyses of the kinase domain of SmRTK-1 confirmed its similarity to IR catalytic domains. However, sequence analysis of the extracellular domain of SmRTK-1 revealed similarity with various proteins (such as drug receptors) that share a structure known as the Venus Flytrap (VFT) module. Alignment with other VFT modules for which the structure has been solved was used to generate a 3D model of the putative VFT module of SmRTK-1. Phylogenetic analysis indicated that the SmRTK-1 VFT module was closer to that of the GABA(B) receptor. Numerous RTK genes recently discovered in vertebrate and invertebrate species code for large families of modular proteins with diverse structures and ligand-binding specificities. SmRTK-1 probably represents a new class of RTK whose function remains to be determined. RTKs are present in all metazoans and associated with the control of metabolism, growth and development. The preferential localization of SmRTK-1 in sporocyst germinal cells and ovocytes could be in favor of its function in schistosome growth and differentiation.
Vicogne
Jérôme
J
Unité INSERM 547, Institut Pasteur Lille, 1 rue du Pr. Calmette, France.
Pin
Jean Philippe
JP
Lardans
Vinca
V
Capron
Monique
M
Noël
Christophe
C
Dissous
Colette
C
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D031257:Droseraceae; D005786:Gene Expression Regulation; D006651:Histocytochemistry; D008018:Life Cycle Stages; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics; D012550:Schistosoma mansoni / Q000201:enzymology* / Q000235:genetics; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D020794:Receptor Protein-Tyrosine Kinases