The ErbB protein family or epidermal growth factor receptor (EGFR) family is a family of four structurally related receptor tyrosine kinases. Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's Disease. In mice loss of signaling by any member of the ErbB family results in embryonic lethality with defects in organs including the lungs, skin, heart and brain. Excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. ErbB-1 and ErbB-2 are found in many human cancers and their excessive signaling may be critical factors in the development and malignancy of these tumors. The ErbB protein family consists of 4 members * ErbB-1, also named epidermal growth factor receptor (EGFR) * ErbB-2, also named HER2 in humans and neu in rodents * ErbB-3, also named HER3 and * ErbB-4, also named HER4 The four members of the ErbB protein family are capable of forming homodimers, heterodimers, and possibly higher order oligomers upon activation by a subset of potential growth factor ligands. Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP673 CPTAC Assay Portal] c42 bfa bf7 aa7 bca a8c bac ddb e96 a2e ae4 ccd c74 da1 d07 b66 d79 parentid=P31749; parentsymbol=AKT1; site=kDGAtMKtFCGtPEy; position=thr308; sitegrpid=447856; ptm=p; direction=u parentid=P31749; parentsymbol=AKT1; site=RPHFPQFsysAsGtA; position=ser473; sitegrpid=447855; ptm=p; direction=u parentid=P31751; parentsymbol=AKT2; site=sDGAtMKtFCGtPEy; position=thr309; sitegrpid=448537; ptm=p; direction=u parentid=Q12778; parentsymbol=FOXO1; site=LPRPRSCtWPLPRPE; position=thr24; sitegrpid=448560; ptm=p; direction=d parentid=P12931; parentsymbol=SRC; site=KLDSGGFyITSRTQF; position=tyr216; sitegrpid=448233; ptm=p; direction=u parentid=Q05397; parentsymbol=FAK; site=RyMEDstyyKAsKGK; position=tyr576; sitegrpid=447889; ptm=p; direction=u parentid=P19174; parentsymbol=PLCG1; site=IGtAEPdyGALyEGR; position=tyr771; sitegrpid=448575; ptm=p; direction=u parentid=Q13541; 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parentsymbol=RAF1; site=IGDFGLAtVksRWsG; position=thr491; sitegrpid=447748; ptm=p; direction=u parentid=Q02750; parentsymbol=MAP2K1; site=LIDsMANsFVGTRSY; position=ser222; sitegrpid=448513; ptm=p; direction=u parentid=Q02750; parentsymbol=MAP2K1; site=VsGQLIDsMANsFVG; position=ser218; sitegrpid=448514; ptm=p; direction=u parentid=P28482; parentsymbol=MAPK1; site=HDHtGFLtEyVAtRW; position=thr185; sitegrpid=447593; ptm=p; direction=u parentid=P28482; parentsymbol=MAPK1; site=HtGFLtEyVAtRWyR; position=tyr187; sitegrpid=447594; ptm=p; direction=u parentid=P27361; parentsymbol=MAPK3; site=HDHtGFLtEyVAtRW; position=thr202; sitegrpid=447542; ptm=p; direction=u parentid=P27361; parentsymbol=MAPK3; site=HtGFLtEyVAtRWyR; position=tyr204; sitegrpid=447543; ptm=p; direction=u parentid=P36507; parentsymbol=MAP2K2; site=VsGQLIDsMANsFVG; position=ser222; sitegrpid=448073; ptm=p; direction=u parentid=P36507; parentsymbol=MAP2K2; site=LIDsMANsFVGTRSY; position=ser226; sitegrpid=448074; ptm=p; direction=u c5e c5e c5e c5e c5e cancer DOID:162 Disease 19419954 PubMed Up-regulation of miR-21 by HER2/neu signaling promotes cell invasion. J Biol Chem 2009 Huang TH Wu F Loeb GB Hsu R Heidersbach A Brincat A Horiuchi D Lebbink RJ Mo YY Goga A McManus MT 20573930 PubMed Case records of the Massachusetts General Hospital. Case 19-2010. A 35-year-old man with adenocarcinoma of the cecum. N Engl J Med 2010 Ryan DP Engelman JA Ferrone CR Sahani DV Lisovsky M 14744244 PubMed ErbB receptors: directing key signaling networks throughout life. Annu Rev Pharmacol Toxicol 2004 Holbro T Hynes NE 17000658 PubMed The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res 2006 Scaltriti M Baselga J 16729045 PubMed A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol 2005 Oda K Matsuoka Y Funahashi A Kitano H 16829981 PubMed EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 2006 Citri A Yarden Y 16729043 PubMed Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol Syst Biol 2005 Schulze WX Deng L Mann M 9872057 PubMed The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events. Bioessays 1998 McCarty JH 14967450 PubMed Signal transduction and oncogenesis by ErbB/HER receptors. Int J Radiat Oncol Biol Phys 2004 Marmor MD Skaria KB Yarden Y 10880430 PubMed The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 2000 Olayioye MA Neve RM Lane HA Hynes NE Alzheimer's disease DOID:10652 Disease epidermal growth factor/neuregulin signaling pathway PW:0000170 Pathway Ontology 10490623 PubMed Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers. Mol Cell Biol 1999 Muthuswamy SK Gilman M Brugge JS 15863494 PubMed ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events. J Biol Chem 2005 Clark DE Williams CC Duplessis TT Moring KL Notwick AR Long W Lane WS Beuvink I Hynes NE Jones FE oxidative phosphorylation pathway PW:0001059 Pathway Ontology 12851486 PubMed Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Cell Cycle 2003 Liang J Slingerland JM 9642287 PubMed Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor. J Biol Chem 1998 Hashimoto Y Katayama H Kiyokawa E Ota S Kurata T Gotoh N Otsuka N Shibata M Matsuda M multiple sclerosis DOID:2377 Disease 16377102 PubMed Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006 Normanno N De Luca A Bianco C Strizzi L Mancino M Maiello MR Carotenuto A De Feo G Caponigro F Salomon DS 15864276 PubMed ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005 Hynes NE Lane HA 11252954 PubMed Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001 Yarden Y Sliwkowski MX 25514926 PubMed PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res 2015 Hornbeck PV Zhang B Murray B Kornhauser JM Latham V Skrzypek E