Faculty Collaboration Database

Identification and molecular characterisation of a gene encoding a member of the insulin receptor family in Echinococcus multilocularis. Int J Parasitol 2003 Mar;33(3):301-12

Date

04/03/2003

Pubmed ID

12670515

DOI

10.1016/s0020-7519(02)00265-5

Scopus ID

2-s2.0-0037350035 (requires institutional sign-in at Scopus site)   80 Citations

Abstract

Receptor kinases play a key role in the communication of cells with their environment and could be important mediators of the effects of host cytokines on endoparasitic organisms. In this paper we describe, for the first time, the characterisation of a receptor tyrosine kinase of the insulin receptor family from a parasitic helminth. Using a degenerative PCR approach, we identified and completely characterised the 5.5kb coding DNA for an Echinococcus multilocularis factor (EmIR) which displays significant homologies to insulin receptors of different phylogenetic origin. EmIR exhibited a domain structure which is typical for the protein family and contained all catalytically important residues at corresponding positions. One striking difference between EmIR and known insulin receptors was the presence of a 172 amino acid insert in the tyrosine kinase region of, as yet, unknown function. In yeast two-hybrid analyses, the ligand binding domains of the human insulin receptor and of EmIR showed comparable affinity to human insulin. The EmIR encoding chromosomal locus (emir) was characterised and comprised 16.5kb. Southern blot hybridisations demonstrated that emir is present as a single copy locus in E. multilocularis. Furthermore, structural comparisons indicated that emir and the insulin receptor genes from mammals and insects derive from a common ancestor. Based on reverse transcriptase-polymerase chain reaction analyses, emir was found to be expressed in the two larval stages metacestode and protoscolex. EmIR is, therefore, likely to play an important role in echinococcal development and possibly also in the interaction with the mammalian host.

Author List

Konrad C, Kroner A, Spiliotis M, Zavala-Góngora R, Brehm K

Author

Antje Kroner-Milsch MD, PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Blotting, Southern
Echinococcus
Genes, Helminth
Humans
Molecular Sequence Data
Parasitology
Polymerase Chain Reaction
Receptor, Insulin
Reverse Transcriptase Polymerase Chain Reaction
Sequence Alignment
Sequence Homology, Amino Acid
Two-Hybrid System Techniques