◀ Back to SMAD4

SMAD4 — SMAD9

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: SMAD4 → Complex of SMAD4-SMAD9 (directlyIncreases, SMAD4/SMAD9 Activity)
  Evidence: Phosphorylation of the C-terminal serine residues in R-Smads by type I receptor kinases is a crucial step in TGF-b family signalling (Abdollah et al., 1997; Macias-Silva et al., 1996; Souchelnytskyi et al., 1997). The two most C-terminal serine residues become phosphorylated and, together with a third, non-phosphorylated serine residue, form an evolutionarily conserved SSXS motif in all R-Smads.... TGF-b and activin receptors phosphorylate Smad2 and Smad3, and BMP receptors phosphorylate Smad1, ...
• OpenBEL Selventa BEL large corpus: Complex of SMAD4-SMAD9 → BMPR1A (increases, SMAD4/SMAD9 Activity)
  Evidence: Phosphorylation of the C-terminal serine residues in R-Smads by type I receptor kinases is a crucial step in TGF-b family signalling (Abdollah et al., 1997; Macias-Silva et al., 1996; Souchelnytskyi et al., 1997). The two most C-terminal serine residues become phosphorylated and, together with a third, non-phosphorylated serine residue, form an evolutionarily conserved SSXS motif in all R-Smads.... TGF-b and activin receptors phosphorylate Smad2 and Smad3, and BMP receptors phosphorylate Smad1, ...
• KEGG TGF-beta signaling pathway: SMAD1/SMAD5/SMAD9 → SMAD4 (protein-protein, activation)
• KEGG TGF-beta signaling pathway: Complex of SMAD1-SMAD4-SMAD5-SMAD9 → ID1/ID2/ID3/ID4 (gene expression, expression)
• KEGG TGF-beta signaling pathway: MAPK1/MAPK3 → Complex of SMAD1-SMAD4-SMAD5-SMAD9 (protein-protein, inhibition)
  
• NCI Pathway Database ALK2 signaling events: SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) → SMAD4 (SMAD4) (modification, collaborate) Visser et al., Mol Endocrinol 2001, Clarke et al., Mol Endocrinol 2001, Macías-Silva et al., J Biol Chem 1998
  Evidence: assay
• NCI Pathway Database ALK2 signaling events: SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) → SMAD4/SMAD1-5-8 (dimer) complex (SMAD4-SMAD1_SMAD9_SMAD5) (modification, collaborate)
  Visser et al., Mol Endocrinol 2001, Clarke et al., Mol Endocrinol 2001, Macías-Silva et al., J Biol Chem 1998
  Evidence: assay
• NCI Pathway Database ALK2 signaling events: SMAD4 (SMAD4) → SMAD4/SMAD1-5-8 (dimer) complex (SMAD4-SMAD1_SMAD9_SMAD5) (modification, collaborate)
  Visser et al., Mol Endocrinol 2001, Clarke et al., Mol Endocrinol 2001, Macías-Silva et al., J Biol Chem 1998
  Evidence: assay
• NCI Pathway Database ALK1 signaling events: SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) → SMAD4 (SMAD4) (modification, collaborate) Oh et al., Proc Natl Acad Sci U S A 2000, Goumans et al., EMBO J 2002, Goumans et al., Mol Cell 2003
• NCI Pathway Database ALK1 signaling events: SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) → SMAD4/SMAD1-5-8 (dimer) complex (SMAD4-SMAD1_SMAD9_SMAD5) (modification, collaborate)
  Oh et al., Proc Natl Acad Sci U S A 2000, Goumans et al., EMBO J 2002, Goumans et al., Mol Cell 2003
• NCI Pathway Database ALK1 signaling events: SMAD4 (SMAD4) → SMAD4/SMAD1-5-8 (dimer) complex (SMAD4-SMAD1_SMAD9_SMAD5) (modification, collaborate)
  Oh et al., Proc Natl Acad Sci U S A 2000, Goumans et al., EMBO J 2002, Goumans et al., Mol Cell 2003
• NCI Pathway Database ALK1 signaling events: SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) → SMAD4 (SMAD4) (modification, collaborate) Scharpfenecker et al., J Cell Sci 2007, Chen et al., J Biol Chem 1999
• NCI Pathway Database ALK1 signaling events: SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) → SMAD4/SMAD1-5-8 (dimer) complex (SMAD4-SMAD1_SMAD9_SMAD5) (modification, collaborate)
  Scharpfenecker et al., J Cell Sci 2007, Chen et al., J Biol Chem 1999
• NCI Pathway Database ALK1 signaling events: SMAD4 (SMAD4) → SMAD4/SMAD1-5-8 (dimer) complex (SMAD4-SMAD1_SMAD9_SMAD5) (modification, collaborate)
  Scharpfenecker et al., J Cell Sci 2007, Chen et al., J Biol Chem 1999
• NCI Pathway Database BMP receptor signaling: SMAD8A (SMAD9) → SMAD4 (SMAD4) (modification, collaborate) Kawai et al., Biochem Biophys Res Commun 2000*
  Evidence: mutant phenotype, physical interaction, other species
• NCI Pathway Database BMP receptor signaling: SMAD8A (SMAD9) → SMAD8A/SMAD8A/SMAD4 complex (SMAD9-SMAD4) (modification, collaborate)
  Kawai et al., Biochem Biophys Res Commun 2000*
  Evidence: mutant phenotype, physical interaction, other species
• NCI Pathway Database BMP receptor signaling: SMAD4 (SMAD4) → SMAD8A/SMAD8A/SMAD4 complex (SMAD9-SMAD4) (modification, collaborate)
  Kawai et al., Biochem Biophys Res Commun 2000*
  Evidence: mutant phenotype, physical interaction, other species
• Reactome Reaction: SMAD4 → SMAD9 (reaction) Qin et al., Mol Cell 2001*, Lagna et al., Nature 1996
• Reactome Reaction: SMAD4 → SMAD9 (direct_complex) Wang et al., Proc Natl Acad Sci U S A 2000*, Xiao et al., J Biol Chem 2001*, Qin et al., Mol Cell 2001*, Xiao et al., Oncogene 2003, Xiao et al., J Biol Chem 2003*, Lagna et al., Nature 1996
• WikiPathways ESC Pluripotency Pathways: Complex of SMAD5-SMAD1-SMAD9-SMAD4 → Complex of SMAD1-SMAD5-SMAD9-SMAD4 (activation)
  
• WikiPathways ESC Pluripotency Pathways: Complex of SMAD5-SMAD1-SMAD9-SMAD4 → MAPK7/MAPK1/MAPK6/MAPK4/MAPK12 (inhibition)
  
• WikiPathways ESC Pluripotency Pathways: SMAD1/SMAD5/SMAD9 → Complex of SMAD5-SMAD1-SMAD9-SMAD4 (activation)
  

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Bind Interaction: SMAD9 — SMAD4 Colland et al., Genome Res 2004
• IRef Bind_translation Interaction: SMAD9 — SMAD4 (two hybrid) Colland et al., Genome Res 2004
• IRef Biogrid Interaction: SMAD9 — SMAD4 (direct interaction, two hybrid) Rual et al., Nature 2005
• IRef Biogrid Interaction: SMAD9 — SMAD4 (physical association, affinity chromatography technology) Nishita et al., Genes Cells 1999*
• IRef Hprd Interaction: SMAD9 — SMAD4 (two hybrid) Colland et al., Genome Res 2004, Rual et al., Nature 2005
• IRef Intact Interaction: SMAD9 — SMAD4 (physical association, two hybrid pooling approach) Rual et al., Nature 2005
• IRef Ophid Interaction: SMAD9 — SMAD4 (aggregation, interologs mapping) Brown et al., Bioinformatics 2005

Text-mined interactions from Literome

Lee et al., Int J Cancer 2001 (Uterine Cervical Neoplasms) : Our findings demonstrate that ( i ) decrease of Smad4 mRNA expression is closely associated with defective TGF-beta response and lack of growth inhibition, ( ii ) activation of PAI-1 by TGF-beta may be Smad4 dependent and ( iii ) the Smad and the p38 cascades are triggered by TGF-beta independently of each other in human cervical cancer
Harada et al., J Biol Chem 2003 : HIPK2 efficiently inhibited Smad1/4 induced transcription from the Smad site containing promoter
Wu et al., J Biol Chem 2003 : Smad4 was required for DACH1 repression of Smad signaling
Jazag et al., Oncogene 2005 (Pancreatic Neoplasms) : Smad4 protein expression was reduced dramatically and TGF-beta-Smad signaling was markedly inhibited in the S4KD cell lines
Schneiders et al., Cardiovasc Res 2005 : Intracellular scavenging of SMAD proteins by transformation of cardiomyocytes with SMAD decoy oligonucleotides or inhibition of SMAD4 synthesis using SMAD4 antisense oligonucleotides reduced the number of apoptotic cells under stimulation with SNAP from 13.3 +/- 1.2 % to control levels ( 8 +/- 1 %, p < 0.05, n = 6 )
Akool et al., J Biol Chem 2005 : Furthermore, activation of the Smad signaling cascade by NO is corroborated by the NO-dependent increase in nuclear Smad-4 level and is paralleled by increased DNA binding of Smad-2/3 containing complexes to a TIMP-1-specific Smad binding element ( SBE )
Matsubara et al., J Biol Chem 2008 : Furthermore, overexpression of Smad1 and Smad4 up-regulated Osterix expression, and an inhibitory Smad , Smad6, markedly suppressed BMP2 induced Osterix expression in the Runx2-deficient cells