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GRB2 — MET

Pathways - manually collected, often from reviews:

• KEGG Pathways in cancer: MET → GRB2 (protein-protein, activation)
• KEGG Renal cell carcinoma: MET → GRB2 (protein-protein, activation)
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer)/GRB2/GAB1 complex (MET-GRB2-GAB1-HGF) → SHP2 (PTPN11) (modification, collaborate) Schaeper et al., J Cell Biol 2000, Maroun et al., Mol Cell Biol 2000
  Evidence: mutant phenotype
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer)/GRB2/GAB1 complex (MET-GRB2-GAB1-HGF) → HGF(dimer)/MET(dimer)/GRB2/GAB1/SHP2 complex (MET-GRB2-GAB1-PTPN11-HGF) (modification, collaborate)
  Schaeper et al., J Cell Biol 2000, Maroun et al., Mol Cell Biol 2000
  Evidence: mutant phenotype
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): SHP2 (PTPN11) → HGF(dimer)/MET(dimer)/GRB2/GAB1/SHP2 complex (MET-GRB2-GAB1-PTPN11-HGF) (modification, collaborate)
  Schaeper et al., J Cell Biol 2000, Maroun et al., Mol Cell Biol 2000
  Evidence: mutant phenotype
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer)/GRB2/GAB1 complex (MET-GRB2-GAB1-HGF) → HGF(dimer)/MET(dimer) complex (MET-HGF) (modification, collaborate)
  Schaeper et al., J Cell Biol 2000, Schaeper et al., Proc Natl Acad Sci U S A 2007, Nguyen et al., J Biol Chem 1997*
  Evidence: assay, physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer)/GRB2/GAB1 complex (MET-GRB2-GAB1-HGF) → GRB2/GAB1 complex (GRB2-GAB1) (modification, collaborate)
  Schaeper et al., J Cell Biol 2000, Schaeper et al., Proc Natl Acad Sci U S A 2007, Nguyen et al., J Biol Chem 1997*
  Evidence: assay, physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer) complex (MET-HGF) → GRB2/GAB1 complex (GRB2-GAB1) (modification, collaborate)
  Schaeper et al., J Cell Biol 2000, Schaeper et al., Proc Natl Acad Sci U S A 2007, Nguyen et al., J Biol Chem 1997*
  Evidence: assay, physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): None → HGF(dimer)/MET(dimer)/GRB2/SOS1 complex (MET-GRB2-SOS1-HGF) (modification, collaborate)
  Schaeper et al., J Cell Biol 2000, Ponzetto et al., Cell 1994, Graziani et al., J Biol Chem 1993
  Evidence: assay
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HRAS/GDP complex (HRAS) → HGF(dimer)/MET(dimer)/GRB2/SOS1 complex (MET-GRB2-SOS1-HGF) (modification, collaborate)
  Schaeper et al., J Cell Biol 2000, Ponzetto et al., Cell 1994, Graziani et al., J Biol Chem 1993
  Evidence: assay
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): Erk1-2 (MAPK3/MAPK1) → HGF(dimer)/MET(dimer)/GRB2/GAB1/SHP2 complex (MET-GRB2-GAB1-PTPN11-HGF) (modification, collaborate)
  Schaeper et al., J Cell Biol 2000, Maroun et al., Mol Cell Biol 2000
  Evidence: mutant phenotype
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): None → HGF(dimer)/MET(dimer)/p52 SHC/GRB2/SOS1 complex (MET-SHC1-GRB2-SOS1-HGF) (modification, collaborate)
  Pelicci et al., Oncogene 1995
  Evidence: assay
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HRAS/GDP complex (HRAS) → HGF(dimer)/MET(dimer)/p52 SHC/GRB2/SOS1 complex (MET-SHC1-GRB2-SOS1-HGF) (modification, collaborate)
  Pelicci et al., Oncogene 1995
  Evidence: assay
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): GRB2 (GRB2) → HGF(dimer)/MET(dimer) complex (MET-HGF) (modification, collaborate)
  Parachoniak et al., J Biol Chem 2009
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): GRB2 (GRB2) → HGF(dimer)/MET(dimer)/GRB2 complex (MET-GRB2-HGF) (modification, collaborate)
  Parachoniak et al., J Biol Chem 2009
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer) complex (MET-HGF) → HGF(dimer)/MET(dimer)/GRB2 complex (MET-GRB2-HGF) (modification, collaborate)
  Parachoniak et al., J Biol Chem 2009
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer)/p52 SHC complex (MET-SHC1-HGF) → GRB2/SOS1 complex (GRB2-SOS1) (modification, collaborate)
  Pelicci et al., Oncogene 1995
  Evidence: physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer)/p52 SHC complex (MET-SHC1-HGF) → HGF(dimer)/MET(dimer)/p52 SHC/GRB2/SOS1 complex (MET-SHC1-GRB2-SOS1-HGF) (modification, collaborate)
  Pelicci et al., Oncogene 1995
  Evidence: physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): GRB2/SOS1 complex (GRB2-SOS1) → HGF(dimer)/MET(dimer)/p52 SHC/GRB2/SOS1 complex (MET-SHC1-GRB2-SOS1-HGF) (modification, collaborate)
  Pelicci et al., Oncogene 1995
  Evidence: physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): EPS15 (EPS15) → HGF(dimer)/MET(dimer)/GRB2 complex (MET-GRB2-HGF) (modification, collaborate)
  Parachoniak et al., J Biol Chem 2009
  Evidence: physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): EPS15 (EPS15) → HGF(dimer)/MET(dimer)/GRB2/EPS15 complex (MET-GRB2-EPS15-HGF) (modification, collaborate)
  Parachoniak et al., J Biol Chem 2009
  Evidence: physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer)/GRB2 complex (MET-GRB2-HGF) → HGF(dimer)/MET(dimer)/GRB2/EPS15 complex (MET-GRB2-EPS15-HGF) (modification, collaborate)
  Parachoniak et al., J Biol Chem 2009
  Evidence: physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer)/GRB2/SOS1 complex (MET-GRB2-SOS1-HGF) → HGF(dimer)/MET(dimer) complex (MET-HGF) (modification, collaborate)
  Higuchi et al., Mol Cell Biol 2004, Ponzetto et al., Cell 1994
  Evidence: assay, physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer)/GRB2/SOS1 complex (MET-GRB2-SOS1-HGF) → GRB2/SOS1 complex (GRB2-SOS1) (modification, collaborate)
  Higuchi et al., Mol Cell Biol 2004, Ponzetto et al., Cell 1994
  Evidence: assay, physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): HGF(dimer)/MET(dimer) complex (MET-HGF) → GRB2/SOS1 complex (GRB2-SOS1) (modification, collaborate)
  Higuchi et al., Mol Cell Biol 2004, Ponzetto et al., Cell 1994
  Evidence: assay, physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): GRB2/SOS1 complex (GRB2-SOS1) → MET/MUC20 complex (MET-MUC20) (modification, collaborate)
  Higuchi et al., Mol Cell Biol 2004, Ponzetto et al., Cell 1994
  Evidence: assay, physical interaction
• WikiPathways Focal Adhesion-PI3K-Akt-mTOR-signaling pathway: FGFR2/KDR/INSR/FGFR3/IGF1R/KIT/FGFR1/EPHA2/EGFR/CSF1R/FGFR4/FLT1/FLT4/NGFR/MET/PDGFRA/PDGFRB/TEK → GRB2 (activation)
• WikiPathways Signaling Pathways in Glioblastoma: IGF1R/ERBB3/FGFR1/PDGFRA/PDGFRB/ERBB2/EGFR/FGFR2/MET → GRB2 (mim-stimulation)

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

Studies that report less than 10 interactions are marked with *

• IRef Biogrid Interaction: MET — GRB2 (physical association, affinity chromatography technology) Goldoni et al., J Cell Biol 2009*
• IRef Biogrid Interaction: MET — GRB2 (direct interaction, pull down) Hill et al., J Exp Ther Oncol 2010*
• IRef Biogrid Interaction: MET — GRB2 (direct interaction, pull down) Ponzetto et al., J Biol Chem 1996*
• IRef Biogrid Interaction: MET — GRB2 (physical association, affinity chromatography technology) Liang et al., Invest Ophthalmol Vis Sci 1998*
• IRef Hprd Interaction: Complex of GRB2-GAB1-MET-MET-GAB1-GRB2-GAB1-MET-GRB2 (in vivo) Schaeper et al., J Cell Biol 2000
• IRef Hprd Interaction: MET — GRB2 (two hybrid) Crostella et al., Oncogene 2001*, Schaaf et al., FASEB J 2005*, Songyang et al., Mol Cell Biol 1994*, Ponzetto et al., J Biol Chem 1996*, Liang et al., Invest Ophthalmol Vis Sci 1998*
• IRef Hprd Interaction: MET — GRB2 (in vitro) Crostella et al., Oncogene 2001*, Schaaf et al., FASEB J 2005*, Songyang et al., Mol Cell Biol 1994*, Ponzetto et al., J Biol Chem 1996*, Liang et al., Invest Ophthalmol Vis Sci 1998*
• IRef Hprd Interaction: MET — GRB2 (in vivo) Crostella et al., Oncogene 2001*, Schaaf et al., FASEB J 2005*, Songyang et al., Mol Cell Biol 1994*, Ponzetto et al., J Biol Chem 1996*, Liang et al., Invest Ophthalmol Vis Sci 1998*
• IRef Ophid Interaction: GRB2 — MET (aggregation, interologs mapping) Brown et al., Bioinformatics 2005

Text-mined interactions from Literome

Bardelli et al., Oncogene 1999 (Cell Transformation, Neoplastic...) : Conversely, MetP13K/Grb2 induced motility, transformation, invasion and metastasis as efficiently as wild type Met
Petrelli et al., Nature 2002 : Cbl, in turn, binds and ubiquitinates activated HGF receptor , and by recruiting the endophilin-CIN85 complex , it regulates receptor internalization
Seiden-Long et al., Carcinogenesis 2008 (Colorectal Neoplasms...) : This suggests that direct Grb2/Shc binding does not contribute to the tumor progression activity of Met receptor