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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-12-24
pubmed:databankReference
pubmed:abstractText
Members of the transforming growth factor-beta/bone morphogenetic protein (TGF-beta/BMP) family of cytokines play crucial roles in animal development and are candidate molecules for host-parasite cross-communication in helminth diseases. TGF-beta/BMP-signalling involves binding of the cytokines to receptor kinases which subsequently activate intracellular transcription factors of the Smad family. We have previously characterized two members of the receptor-regulated Smad (R-Smad) family, EmSmadA and EmSmadB, from the human parasitic cestode Echinococcus multilocularis and now present evidence for two additional Smads that are expressed by the larval stages of the parasite. The full-length cDNAs coding for a third R-Smad, EmSmadC, and a common mediator Smad (Co-Smad), EmSmadD, were characterized. While EmSmadD displayed a typical Co-Smad structure, EmSmadC lacked the N-terminal MH1 domain which is typically found in Smads. In yeast two-hybrid analyses, EmSmadC and EmSmadD were capable of homo- and heterodimer formation with other Echinococcus Smads. Furthermore, EmSmadC displayed autonomous transcription activation activity and interacted with EmSkip, a member of the SNW/SKIP family of transcriptional regulators. In a heterologous expression system, EmSmadC was specifically phosphorylated by mammalian TGF-beta receptors, indicating that it is a member of the AR-Smad sub-family. Finally, in activity assays, the parasite's Erk-like kinase EmMPK1 phosphorylated EmSmadD, indicating cross-regulation between mitogen-activated protein kinase cascade- and TGF-beta/BMP-signalling in Echinococcus. The data presented herein significantly broaden our knowledge of Smad-signalling factors in E. multilocularis and will facilitate studies on TGF-beta/BMP-regulated genes in the parasite as well as TGF-beta/BMP mediated host-parasite cross-interaction during alveolar echinococcosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0020-7519
pubmed:author
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
161-76
pubmed:meshHeading
pubmed-meshheading:17845804-Amino Acid Sequence, pubmed-meshheading:17845804-Animals, pubmed-meshheading:17845804-Base Sequence, pubmed-meshheading:17845804-Bone Morphogenetic Proteins, pubmed-meshheading:17845804-Cloning, Molecular, pubmed-meshheading:17845804-Echinococcosis, pubmed-meshheading:17845804-Echinococcus multilocularis, pubmed-meshheading:17845804-Genes, Helminth, pubmed-meshheading:17845804-Host-Parasite Interactions, pubmed-meshheading:17845804-Humans, pubmed-meshheading:17845804-Larva, pubmed-meshheading:17845804-Molecular Sequence Data, pubmed-meshheading:17845804-Protein Structure, Tertiary, pubmed-meshheading:17845804-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17845804-Sequence Alignment, pubmed-meshheading:17845804-Smad Proteins, pubmed-meshheading:17845804-Smad4 Protein, pubmed-meshheading:17845804-Transforming Growth Factor beta, pubmed-meshheading:17845804-Two-Hybrid System Techniques
pubmed:year
2008
pubmed:articleTitle
Molecular characterisation of a second structurally unusual AR-Smad without an MH1 domain and a Smad4 orthologue from Echinococcus multilocularis.
pubmed:affiliation
University of Würzburg, Institute of Hygiene and Microbiology, Josef-Schneider-Strasse 2, D-97080 Würzburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't