IndraLab
Statements
reach
"Recently, the studies by Sekimoto et al and Matsuzaki et al have shown that TGF-beta type I receptor (TbetaRI) phosphorylates Smad3 at the COOH-terminal (pSmad3C) thus inhibiting cell proliferation by up-regulating p21 WAF1 in human gastric mucosa epithelial cells (RGM1) and human intestinal epithelial cells; the activated c-Jun N-terminal kinase (JNK) phosphorylates Smad3 at the Linker-terminal Ser 213 site (pSmad3L) to promote cell proliferation and carcinogenesis by up-regulating c-Myc in Ras transformed human RGM1 cells and colon cancer cells [XREF_BIBR, XREF_BIBR]."
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"NAR effectively preserved basal MMP activity levels and prevented TGF-beta activation; (3) TGF-beta binds to the TGF-beta type II receptor (TbetaRII), which recruits and phosphorylates the TGF-beta type I receptor (TbetaRI), which in turn phosphorylates Smad3 in its C-terminal region, leading to pSmad3C formation."
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"Domain specific phospho-Smad2/3 Abs have allowed us to reveal that TbetaRI and JNK differentially phosphorylate Smad2 and Smad3 to create three phosphorylated forms (phosphoisoforms) : COOH-terminally-phosphorylated Smad (pSmad2C and pSmad3C), linker phosphorylated Smad (pSmad2L and pSmad3L) and dually phosphorylated Smad (pSmad2L/C and pSmad3L/C) [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"In this study, we showed that a small-molecule inhibitor of ALK5, IN-1130, successfully blocked TGF-beta1-induced signaling, i.e., phosphorylation and nuclear translocation of Smad2 and Smad3, and inhibited extracellular matrix production in fibroblasts derived from human PD plaque."
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"TGF-beta signaling in hepatocyte is implicated in liver fibrosis and carcinogenesis.While the C-terminal phosphorylation of SMAD3 by TGFBR1 may be tumor-suppressive, oncogenic linker phosphorylated SMAD3signaling is involved in both nonalcoholic steatohepatitis-relatedHCC and HBV and HCV related HCC [XREF_BIBR - XREF_BIBR]."
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"Connection of TGF-beta to TbetaRII (type II TGFbeta receptor) activates this kinase subunit, increases affinity to TbetaRI (type I TGFbeta receptor) and, consequently, activates TbetaRI which stimulates phosphorylation of the Smad-3 protein attached to the 3-endosomal SARA protein [XREF_BIBR]."
sparser
"Considering that ALK5-dependent Smad3 phosphorylation is central to the canonical TGF-β signaling, we assessed the effects of FLIL33 overexpression, stimulation with rhTGF-β, and the combination of this stimuli on the transcriptome of a NHLF culture utilizing the RNA-Seq approach."
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"Moreover, Igf2bp2 overexpression promoted the phosphorylation of SMAD2/SMAD3, AKT, and PI3K, whereas Tgfbr1 knockdown exhibited the opposite effect; Tgfbr1 knockdown also partially attenuated the effects of Igf2bp2 overexpression on the phosphorylation of SMAD2/SMAD3, AKT, and PI3K."
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"When TGF-beta signaling is initiated, the activated TGF-beta type I receptor phosphorylates the downstream signaling mediators Smad2 and Smad3, which then bind to Smad4 and translocate into the nucleus, where they act as transcription factors activating the expression of TGF-beta response genes involved in EMT."
sparser
"Activated Alk5 induces the phosphorylation of Smad2 and Smad3 and activation of Alk5/Smad2/3 pathway leads to inhibition of cell proliferation and is associated with a mature endothelium with increased expression of genes such as plasminogen activator inhibitor-1 (PAI-1), collagen type I (Col-1)."
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"Addition of SB431542, a selective inhibitor of activin receptor like kinases ALK4, ALK5 and ALK7, which has been shown to inhibit cardiomyogenesis when added during the early phase of differentiation (either Day 0 or Day 2) [XREF_BIBR], prevented TGFbeta-SMAD2 and SMAD3 activation and phosphorylation, as expected, demonstrating a stage- and time dependent reduction in RFP + -CMs."
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"TGFBR1 and TGFBR2 are proteins that phosphorylate members of the SMAD family (SMAD-2 and SMAD-3) and induce the formation of a complex with the SMAD-4 member; subsequently, this SMAD complex is translocated to the nucleus and regulates the transcription of TGF- β target genes [112]."
sparser
"Upon activation, the TGF-beta type I receptor phosphorylates Smad2 and Smad3, which then form complexes with Smad4 and accumulate in the nucleus to regulate transcription of a variety of genes that encode crucial determinants of cell fate, such as cell cycle components, differentiation factors and cell adhesion molecules."
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"In TGF-beta1-stimulated renal tubular epithelial cells and interstitial fibroblast cells, GQ5 inhibited the interaction of Smad3 with TGF-beta type I receptor (TbetaRI) by blocking binding of Smad3 to SARA, suppressed subsequent phosphorylation of Smad3, reduced nuclear translocation of Smad2, Smad3, and Smad4, and downregulated the transcription of major fibrotic genes such as alpha-smooth muscle actin (alpha-SMA), collagen I, and fibronectin."
sparser
"In chondrocytes ALK1 has been identified as a TGF-β receptor.[ xref xref ] Activation of ALK5 stimulates phosphorylation of Smad2 and Smad3 while ALK1 activates the Smad1/5/8 pathway.[ xref xref ] Phosphorylated R-Smads form heterotrimers with Smad4 and this complex is transported to the nucleus."
rlimsp
"Upon activation, the TGF-beta type I receptor phosphorylates Smad2 and Smad3, which then form complexes with Smad4 and accumulate in the nucleus to regulate transcription of a variety of genes that encode crucial determinants of cell fate, such as cell cycle components, differentiation factors and cell adhesion molecules."
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"In that the preceding data show that disrupting basolateral targeting of TbetaRI, per se, has no demonstrable impact on the ability of TbetaRI (in the context of wild-type TbetaRII) to activate Smad3 phosphorylation, we next investigated whether TGFbetaRs expressed on the apical surface would be able to similarly stimulate Smad3 activation as endogenous basolateral receptors."
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"Upon activation, the TGF-beta type I receptor phosphorylates Smad2 and Smad3, which then form complexes with Smad4 and accumulate in the nucleus to regulate transcription of a variety of genes that encode crucial determinants of cell fate, such as cell cycle components, differentiation factors and cell adhesion molecules."
sparser
"In the presence of activated ALK5 signaling, the overexpression of the wild-type Smad3 and the Smad3 (S3D) mutant, but not Smad3 (S3A), repressed Nur77 transactivation ( xref ), suggesting a requirement of ALK5-induced phosphorylation of Smad3 for the repression of Nur77 transactivation."
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"Indirect crosstalk between SMAD and STAT was first reported as the inhibition of Smad3/4 mediated TGF-beta signalling by Jak1-STAT1-mediated interferon (IFN)-gamma signalling via induction of the inhibitory Smad, Smad7, which prevents TbetaRI induced C-terminal phosphorylation of Smad3."
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"SB functions via specifically inhibiting the ability of the Activin and Nodal receptors, Alk4 and Alk7, and the TGFbeta receptor, Alk5, to phosphorylate Smad2 and Smad3 XREF_BIBR, which is necessary for subsequent translocation to the nucleus for initiation of downstream signaling XREF_BIBR."
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"To address that issue, kinetic experiments were performed that combined parallel examination of TbetaRI, TbetaRII, and E-cadherin surface expression, together with the capacity of TGF-beta to induce both SMAD3 phosphorylation and target gene induction at various time points following cell seeding."