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BTC — EGFR

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: Complex of EGFR-ERBB2 → BTC (directlyIncreases)
  Evidence: the second group betacellulin (BTC), heparin-binding EGF (HB-EGF), and epiregulin (EPR), which exhibit dual specificity in that they bind ErbB1 and ErbB4.
• OpenBEL Selventa BEL large corpus: Complex of EGFR-ERBB3 → BTC (directlyIncreases)
  Evidence: the second group betacellulin (BTC), heparin-binding EGF (HB-EGF), and epiregulin (EPR), which exhibit dual specificity in that they bind ErbB1 and ErbB4.
• OpenBEL Selventa BEL large corpus: Complex of EGFR-ERBB4 → BTC (directlyIncreases)
  Evidence: the second group betacellulin (BTC), heparin-binding EGF (HB-EGF), and epiregulin (EPR), which exhibit dual specificity in that they bind ErbB1 and ErbB4.
• OpenBEL Selventa BEL large corpus: EGFR → BTC (increases) Shin et al., Circ Res 2003*
  Evidence: BTC induced phosphorylation of all four EGF receptors present on HTASMCs: ErbB1, ErbB2, ErbB3, and ErbB4.
• KEGG ErbB signaling pathway: BTC → Complex of EGFR (protein-protein, activation)
• KEGG ErbB signaling pathway: BTC → EGFR (protein-protein, activation)
• NCI Pathway Database ErbB receptor signaling network: betacellulin (BTC) → EGFR (EGFR) (modification, collaborate) Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: betacellulin (BTC) → EGFR/ErbB2/betacellulin complex (EGFR-ERBB2-BTC) (modification, collaborate)
  Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR (EGFR) → EGFR/ErbB2/betacellulin complex (EGFR-ERBB2-BTC) (modification, collaborate)
  Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR/ErbB2/betacellulin complex (EGFR-ERBB2-BTC) → ErbB2 (ERBB2) (modification, collaborate) Riese et al., J Biol Chem 1996
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: betacellulin (BTC) → EGFR (EGFR) (modification, collaborate) Saito et al., Endocrinology 2004*, Riese et al., Oncogene 1996*
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: betacellulin (BTC) → EGFR/EGFR/betacellulin/betacellulin complex (EGFR-BTC) (modification, collaborate)
  Saito et al., Endocrinology 2004*, Riese et al., Oncogene 1996*
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB receptor signaling network: EGFR (EGFR) → EGFR/EGFR/betacellulin/betacellulin complex (EGFR-BTC) (modification, collaborate)
  Saito et al., Endocrinology 2004*, Riese et al., Oncogene 1996*
  Evidence: assay, physical interaction
• Reactome Reaction: BTC → EGFR (reaction) Vijapurkar et al., Exp Cell Res 2003, Walton et al., J Biol Chem 1990, Li et al., Cell Signal 2007, Xu et al., Mol Cell Biol 2007, Hazan et al., Cell Growth Differ 1990, Kaushansky et al., Chem Biol 2008, Helin et al., J Biol Chem 1991, Margolis et al., J Biol Chem 1989, Ricci et al., Oncogene 1995, Wallasch et al., EMBO J 1995, Prigent et al., EMBO J 1994, Soler et al., Oncogene 1994, Segatto et al., Oncogene 1993, Cohen et al., J Biol Chem 1996, Pinkas-Kramarski et al., EMBO J 1996
• Reactome Reaction: BTC → EGFR (indirect_complex) Cohen et al., J Biol Chem 1996

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

Studies that report less than 10 interactions are marked with *

• IRef Dip Interaction: BTC — EGFR (physical association, coimmunoprecipitation) Ishiyama et al., Diabetologia 1998*
• IRef Hprd Interaction: BTC — EGFR (in vivo) Mixan et al., Oncogene 1998*
• IRef Ophid Interaction: BTC — EGFR (aggregation, interologs mapping) Brown et al., Bioinformatics 2005

Text-mined interactions from Literome

Yamanaka et al., Biochem Biophys Res Commun 2001 : Among four EGF-receptor (EGFR) family members, the EGFR was solely activated by EGF, heparin binding EGF (HB-EGF), transforming growth factor alpha ( TGF alpha ), epiregulin (ER), and betacellulin (BTC) , resulting in induction of phenotypic modulation of SMCs
Saito et al., Endocrinology 2004 : Expression of a dominant interfering MEK kinase 1 (MEKK1) and Y1068F EGFR more efficiently blocked the enhanced Erk activation by BTC , compared with EGF
O-charoenrat et al., Int J Cancer 2004 (Carcinoma, Squamous Cell...) : Taken together, our data show that BTC induces MMP-9 production and invasion primarily through activation of EGFR , MAPK and PI3K/Akt in HNSCC cells
Stern et al., Biochem J 2008 : EGF ( 17 nM ) and BTC ( 8.5 nM ) induced significant EGF-R degradation, with or without ectopic expression of the ubiquitin ligase Cbl
Guo et al., Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2011 : EGFR ligands BTC can increase proliferation and neogenesis
Riese et al., Oncogene 1996 : In the cell lines expressing a single erbB family receptor, betacellulin not only stimulated EGFR tyrosine phosphorylation, but it activated erbB-4 as well
Modjtahedi et al., Biochem Biophys Res Commun 1996 : We show that one of these mAbs ( ICR62 ) also prevents activation of the EGFR by betacellulin as evidenced by reversal of the effects on the growth of human fibroblasts and the head and neck carcinoma cell line HN5 and by inhibition of receptor phosphorylation in HN5 cells
Mixan et al., Oncogene 1998 (Breast Neoplasms...) : BTC-TX50 induced tyrosine phosphorylation of both EGFR and HER4, whereas BTC-TX48 induced phosphorylation of HER4 but to a much lesser extent EGFR, indicating that the presence of two additional amino acid residues, Arg62 and Lys63, contribute to full kinase activity