%0 Journal Article %1 zavala-gongora_molecular_2008 %A Zavala-Góngora, Ricardo %A Derrer, Bianca %A Gelmedin, Verena %A Knaus, Petra %A Brehm, Klaus %D 2008 %J International Journal for Parasitology %K Acid Alignment, Amino Animals, Base Bone Chain Cloning, Data, Echinococcosis, Echinococcus Factor Genes, Growth Helminth, Humans, Interactions, Larva, Molecular Molecular, Morphogenetic Polymerase Protein Protein, Proteins, Reaction, Reverse Sequence Sequence, Smad Smad4 Structure, System Techniques Tertiary, Transcriptase Transforming ag_brehm beta, multilocularis, {Host-Parasite} {Two-Hybrid} %N 2 %P 161--176 %R 10.1016/j.ijpara.2007.07.008 %T Molecular characterisation of a second structurally unusual AR-Smad without an MH1 domain and a Smad4 orthologue from Echinococcus multilocularis %U http://www.ncbi.nlm.nih.gov/pubmed/17845804 %V 38 %X 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.

@article{zavala-gongora_molecular_2008, abstract = {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.}, added-at = {2011-04-07T15:44:20.000+0200}, author = {{Zavala-Góngora}, Ricardo and Derrer, Bianca and Gelmedin, Verena and Knaus, Petra and Brehm, Klaus}, biburl = {https://www.bibsonomy.org/bibtex/214e9df6ad68b54dd08c9ebd5f7f77532/hymi}, doi = {10.1016/j.ijpara.2007.07.008}, interhash = {f2851addf2d5e15ab23ca9313cb93c68}, intrahash = {14e9df6ad68b54dd08c9ebd5f7f77532}, issn = {0020-7519}, journal = {International Journal for Parasitology}, keywords = {Acid Alignment, Amino Animals, Base Bone Chain Cloning, Data, Echinococcosis, Echinococcus Factor Genes, Growth Helminth, Humans, Interactions, Larva, Molecular Molecular, Morphogenetic Polymerase Protein Protein, Proteins, Reaction, Reverse Sequence Sequence, Smad Smad4 Structure, System Techniques Tertiary, Transcriptase Transforming ag_brehm beta, multilocularis, {Host-Parasite} {Two-Hybrid}}, month = feb, note = {{PMID:} 17845804}, number = 2, pages = {161--176}, timestamp = {2011-04-07T16:35:57.000+0200}, title = {Molecular characterisation of a second structurally unusual {AR-Smad} without an {MH1} domain and a Smad4 orthologue from Echinococcus multilocularis}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17845804}, volume = 38, year = 2008 }