Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. 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. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. 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. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.Isoform 2 may act as an antagonist of EGF action.

• GO:0043006 : activation of phospholipase A2 activity by calcium-mediated signaling
• GO:0007202 : activation of phospholipase C activity
• GO:0007411 : axon guidance
• GO:0008283 : cell proliferation
• GO:0016337 : cell-cell adhesion
• GO:0021795 : cerebral cortex cell migration
• GO:0048546 : digestive tract morphogenesis
• GO:0001892 : embryonic placenta development
• GO:0001942 : hair follicle development
• GO:0060571 : morphogenesis of an epithelial fold
• GO:0043066 : negative regulation of apoptotic process
• GO:0042059 : negative regulation of epidermal growth factor receptor signaling pathway
• GO:0042177 : negative regulation of protein catabolic process
• GO:0001503 : ossification
• GO:0035413 : positive regulation of catenin import into nucleus
• GO:0030335 : positive regulation of cell migration
• GO:0031659 : positive regulation of cyclin-dependent protein kinase activity involved in G1/S
• GO:0045739 : positive regulation of DNA repair
• GO:0045740 : positive regulation of DNA replication
• GO:0050679 : positive regulation of epithelial cell proliferation
• GO:0048146 : positive regulation of fibroblast proliferation
• GO:0043406 : positive regulation of MAP kinase activity
• GO:0045429 : positive regulation of nitric oxide biosynthetic process
• GO:0051897 : positive regulation of protein kinase B signaling cascade
• GO:0046777 : protein autophosphorylation
• GO:0051205 : protein insertion into membrane
• GO:0050999 : regulation of nitric-oxide synthase activity
• GO:0050730 : regulation of peptidyl-tyrosine phosphorylation
• GO:0006950 : response to stress
• GO:0070141 : response to UV-A
• GO:0007435 : salivary gland morphogenesis

Source: The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet.. May 2000;25(1):25-9.
World Wide Web URL: http://www.geneontology.org/

• OMIM:131550 : Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in (OMIM:211980 )
• OMIM:131550 : Adenocarcinoma of lung, response to tyrosine kinase inhibitor in (OMIM:211980 )
• OMIM:131550 : Nonsmall cell lung cancer, susceptibility to (OMIM:211980 )

Source: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), May, 2012.
World Wide Web URL: http://omim.org/