scholarly journals Interplay of Signal Mediators of Decapentaplegic (Dpp): Molecular Characterization of Mothers against dpp, Medea, and Daughters against dpp

1998 ◽  
Vol 9 (8) ◽  
pp. 2145-2156 ◽  
Author(s):  
Hirofumi Inoue ◽  
Takeshi Imamura ◽  
Yasuhiro Ishidou ◽  
Masao Takase ◽  
Yoshiyuki Udagawa ◽  
...  

Decapentaplegic (Dpp) plays an essential role inDrosophila development, and analyses of the Dpp signaling pathway have contributed greatly to understanding of the actions of the TGF-β superfamily. Intracellular signaling of the TGF-β superfamily is mediated by Smad proteins, which are now grouped into three classes. Two Smads have been identified inDrosophila. Mothers against dpp (Mad) is a pathway-specific Smad, whereas Daughters against dpp (Dad) is an inhibitory Smad genetically shown to antagonize Dpp signaling. Here we report the identification of a common mediator Smad inDrosophila, which is closely related to human Smad4. Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. Dad stably associates with Tkv and thereby inhibits Tkv-induced Mad phosphorylation. Dad also blocks hetero-oligomerization and nuclear translocation of Mad. We also show that Mad exists as a monomer in the absence of Tkv stimulation. Tkv induces homo-oligomerization of Mad, and Dad inhibits this step. Finally, we propose a model for Dpp signaling by Drosophila Smad proteins.

Cell Reports ◽  
2018 ◽  
Vol 25 (5) ◽  
pp. 1304-1317.e5 ◽  
Author(s):  
Yumeng Wang ◽  
Xiaoyan Xu ◽  
Dejan Maglic ◽  
Michael T. Dill ◽  
Kamalika Mojumdar ◽  
...  

2010 ◽  
Vol 30 (2) ◽  
pp. 81-88 ◽  
Author(s):  
Qinghua Xue ◽  
Limin Yang ◽  
Xiaoling Liu ◽  
Wenjun Liu

2012 ◽  
Vol 9 (1) ◽  
pp. 278 ◽  
Author(s):  
Amer Alazawy ◽  
Siti Suri Arshad ◽  
Abdul Rahman Omar ◽  
Mohd Hair Bejo ◽  
Faruku Bande ◽  
...  

2010 ◽  
Vol 84 (21) ◽  
pp. 11045-11055 ◽  
Author(s):  
Deendayal Patel ◽  
Yuchen Nan ◽  
Meiyan Shen ◽  
Krit Ritthipichai ◽  
Xiaoping Zhu ◽  
...  

ABSTRACT Type I interferons (IFNs) IFN-α/β play an important role in innate immunity against viral infections by inducing antiviral responses. Porcine reproductive and respiratory syndrome virus (PRRSV) inhibits the synthesis of type I IFNs. However, whether PRRSV can inhibit IFN signaling is less well understood. In the present study, we found that PRRSV interferes with the IFN signaling pathway. The transcript levels of IFN-stimulated genes ISG15 and ISG56 and protein level of signal transducer and activator of transcription 2 (STAT2) in PRRSV VR2385-infected MARC-145 cells were significantly lower than those in mock-infected cells after IFN-α treatment. IFN-induced phosphorylation of both STAT1 and STAT2 and their heterodimer formation in the PRRSV-infected cells were not affected. However, the majority of the STAT1/STAT2/IRF9 (IFN regulatory factor 9) heterotrimers remained in the cytoplasm of PRRSV-infected cells, which indicates that the nuclear translocation of the heterotrimers was blocked. Overexpression of NSP1β of PRRSV VR2385 inhibited expression of ISG15 and ISG56 and blocked nuclear translocation of STAT1, which suggests that NSP1β might be the viral protein responsible for the inhibition of IFN signaling. PRRSV infection in primary porcine pulmonary alveolar macrophages (PAMs) also inhibited IFN-α-stimulated expression of the ISGs and the STAT2 protein. In contrast, a licensed low-virulence vaccine strain, Ingelvac PRRS modified live virus (MLV), activated expression of IFN-inducible genes, including those of chemokines and antiviral proteins, in PAMs without the addition of external IFN and had no detectable effect on IFN signaling. These findings suggest that PRRSV interferes with the activation and signaling pathway of type I IFNs by blocking ISG factor 3 (ISGF3) nuclear translocation.


Author(s):  
Jennifer L. Green ◽  
Robin Osterhout ◽  
Amy L. Klova ◽  
Carsten Merkwirth ◽  
Scott R.P. McDonnell ◽  
...  

1987 ◽  
Vol 10 (2) ◽  
pp. 117-126 ◽  
Author(s):  
Carmen Castresana ◽  
Roberto Staneloni ◽  
Vedpal S. Malik ◽  
Anthony R. Cashmore

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