ERBIN is a new SARA-interacting protein: competition between SARA and SMAD2 and SMAD3 for binding to ERBIN (Journal article)

Sflomos, G./ Kostaras, E./ Panopoulou, E./ Pappas, N./ Kyrkou, A./ Politou, A. S./ Fotsis, T./ Murphy, C.

SARA, an early endosomal protein, plays a key role in TGFbeta signalling, as it presents SMAD2 and SMAD3 for phosphorylation by the activated TGFbeta receptors. Here, we show that ERBIN is a new SARA-interacting protein that can be recruited by SARA to early endosomes. ERBIN was recently shown to bind and segregate phosphorylated SMAD2 and SMAD3 (SMAD2/3) in the cytoplasm, thereby inhibiting SMAD2/3-dependent transcription. SARA binds to ERBIN using a new domain, which we have called the ERBID (ERBIN-binding domain), whereas ERBIN binds to SARA using a domain (amino acids 1208-1265) that also interacts with SMAD2 and SMAD3, which we have called the SSID (SARA- and SMAD-interacting domain). We additionally show that SARA competes with SMAD2/3 for binding to ERBIN. In agreement, overexpression of SARA or the ERBID peptide reverses the inhibitory effect of ERBIN on SMAD2/3-dependent transcription. Taken together, these data suggest that the response of cells to TGFbeta and activin A can be influenced by the relative concentrations of SARA, ERBIN and SMAD2/3.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Activins/metabolism,Adaptor Proteins, Signal Transducing/chemistry/genetics/*metabolism,Animals,Cell Line,Cell Nucleus/metabolism,Genes, Reporter,Humans,Intracellular Signaling Peptides and Proteins/chemistry/genetics/*metabolism,Luciferases, Renilla/biosynthesis/genetics,Mice,Peptide Fragments/metabolism,Protein Binding,Protein Interaction Domains and Motifs,Protein Transport,RNA Interference,Response Elements,Serine Endopeptidases/chemistry/genetics/*metabolism,Smad2 Protein/*metabolism,Smad3 Protein/*metabolism,Transcriptional Activation,Transforming Growth Factor beta/metabolism
ISSN: 1477-9137
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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