Part:BBa_K4040035

Truncated EGFR

Sequence and Features

Assembly Compatibility:

• 10
  INCOMPATIBLE WITH RFC[10]

  Illegal PstI site found at 79
  Illegal PstI site found at 238
  Illegal PstI site found at 346
  
• 12
  INCOMPATIBLE WITH RFC[12]

  Illegal PstI site found at 79
  Illegal PstI site found at 238
  Illegal PstI site found at 346
  Illegal NotI site found at 587
  Illegal NotI site found at 1208
  Illegal NotI site found at 1520
  
• 21
  INCOMPATIBLE WITH RFC[21]

  Illegal BamHI site found at 1089
  
• 23
  INCOMPATIBLE WITH RFC[23]

  Illegal PstI site found at 79
  Illegal PstI site found at 238
  Illegal PstI site found at 346
  
• 25
  INCOMPATIBLE WITH RFC[25]

  Illegal PstI site found at 79
  Illegal PstI site found at 238
  Illegal PstI site found at 346
  
• 1000
  COMPATIBLE WITH RFC[1000]

Usage and Biology

It is the receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses[1]. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF[2]. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. EGFR activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules[3]. It may also activate the NF-kappa-B signaling cascade[4]. EGFR also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling[5]. It phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin[6]. EGFR positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration[7].

References

[1]Chen WS, Lazar CS, Lund KA, Welsh JB, Chang CP, Walton GM, Der CJ, Wiley HS, Gill GN, Rosenfeld MG. Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation. Cell. 1989 Oct 6;59(1):33-43. doi: 10.1016/0092-8674(89)90867-2. PMID: 2790960.

[2]Chen WS, Lazar CS, Lund KA, Welsh JB, Chang CP, Walton GM, Der CJ, Wiley HS, Gill GN, Rosenfeld MG. Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation. Cell. 1989 Oct 6;59(1):33-43. doi: 10.1016/0092-8674(89)90867-2. PMID: 2790960.

[3]Runkle KB, Kharbanda A, Stypulkowski E, Cao XJ, Wang W, Garcia BA, Witze ES. Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on EGFR Signaling. Mol Cell. 2016 May 5;62(3):385-396. doi: 10.1016/j.molcel.2016.04.003. PMID: 27153536; PMCID: PMC4860254.

[4]Habib AA, Chatterjee S, Park SK, Ratan RR, Lefebvre S, Vartanian T. The epidermal growth factor receptor engages receptor interacting protein and nuclear factor-kappa B (NF-kappa B)-inducing kinase to activate NF-kappa B. Identification of a novel receptor-tyrosine kinase signalosome. J Biol Chem. 2001 Mar 23;276(12):8865-74. doi: 10.1074/jbc.M008458200. Epub 2000 Dec 14. PMID: 11116146.

[5]Derrien A, Druey KM. RGS16 function is regulated by epidermal growth factor receptor-mediated tyrosine phosphorylation. J Biol Chem. 2001 Dec 21;276(51):48532-8. doi: 10.1074/jbc.M108862200. Epub 2001 Oct 15. PMID: 11602604.

[6]Li Y, Ren J, Yu W, Li Q, Kuwahara H, Yin L, Carraway KL 3rd, Kufe D. The epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin. J Biol Chem. 2001 Sep 21;276(38):35239-42. doi: 10.1074/jbc.C100359200. Epub 2001 Aug 1. PMID: 11483589.

[7]Ghosh P, Beas AO, Bornheimer SJ, Garcia-Marcos M, Forry EP, Johannson C, Ear J, Jung BH, Cabrera B, Carethers JM, Farquhar MG. A G{alpha}i-GIV molecular complex binds epidermal growth factor receptor and determines whether cells migrate or proliferate. Mol Biol Cell. 2010 Jul 1;21(13):2338-54. doi: 10.1091/mbc.e10-01-0028. Epub 2010 May 12. PMID: 20462955; PMCID: PMC2893996.