title: ERBIN is a new SARA-interacting protein: competition between SARA and SMAD2 and SMAD3 for binding to ERBIN.
abstract: SARA, an early endosomal protein, plays a key role in TGFβ signalling, as it presents SMAD2 and SMAD3 for phosphorylation by the activated TGFβ 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 TGFβ and activin A can be influenced by the relative concentrations of SARA, ERBIN and SMAD2/3.
authors: Laboratory of Biological Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece.
authors: George
authors: G
authors: Sflomos
authors: Eleftherios
authors: E
authors: Kostaras
authors: Ekaterini
authors: E
authors: Panopoulou
authors: Nikolaos
authors: N
authors: Pappas
authors: Athena
authors: A
authors: Kyrkou
authors: Anastasia S
authors: AS
authors: Politou
authors: Theodore
authors: T
authors: Fotsis
authors: Carol
authors: C
authors: Murphy
mesh_terms: D028341:Activins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D034622:RNA Interference; D020218:Response Elements; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C413364:ERBIN protein, human; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; C422405:activin A; D028341:Activins; D049410:Luciferases, Renilla; C116420:ZFYVE16 protein, human; D012697:Serine Endopeptidases