ErbB Signaling Pathway (Homo sapiens)

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ER DNA Cell cycle progression (EGFR) Receptor ubiquitylation Proliferation Angiogenesis Non-small cell lung cancer Activation by ErbB2 overexpression (cancers) Degradation Survival Metabolism Cellular targets Pancreatic Cancer Adhesion Protein synthesis Colon cancer Adhesion Migration No signaling DNA Differentiation Endometrial cancer (HER2/ Neu) DNA Migration / Invasion Glioma Cell survival DNA Cellular targets P SHC Cell Cycle P GSK3 NRG4 MDM2 PI3K ERBB4 Calcium Signaling Pathway AKT3 P PLCG BTC P JNK p53 ERBB3 NRG1 ARAF P BAD GAB1 SOS IP3 SRC BIM GRB2 NRG3 MAPK Signaling Pathway MIR21 EREG GRB2 P STAT5 P p21 P MEK1 ERBB4 HBEGF PIP3 P eIF-4EBP Ca2+ ERBB2 MIR21 P CRK ERBB2 ERBB4 PRKCA P P70S6K p27 CAMK2A Diacylglycerol PDK1 P mTOR Apoptosis P STAT5 PIP2 P CBL PAK4 NCK Jnkk2 P ERK P FAK ABL mTor Signaling Pathway NRG2 P FOXO1 AREG TGFA EGF ERBB1 ERBB1 ERBB2 ERBB1 P JUN P ELK ERBB2 ERBB2 ERBB3 ERBB3 HRAS KRAS P ELK P Myc MYC CCND1 Name: ErbB Signaling Pathway License: CC BY 2.0 Organism: Homo sapiens


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.

Based on KEGG.

Quality Tags

Ontology Terms



  1. Ryan DP, Engelman JA, Ferrone CR, Sahani DV, Lisovsky M; ''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 PubMed
  2. Hashimoto Y, Katayama H, Kiyokawa E, Ota S, Kurata T, Gotoh N, Otsuka N, Shibata M, Matsuda M; ''Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor.''; J Biol Chem, 1998 PubMed
  3. Oda K, Matsuoka Y, Funahashi A, Kitano H; ''A comprehensive pathway map of epidermal growth factor receptor signaling.''; Mol Syst Biol, 2005 PubMed
  4. Huang TH, Wu F, Loeb GB, Hsu R, Heidersbach A, Brincat A, Horiuchi D, Lebbink RJ, Mo YY, Goga A, McManus MT; ''Up-regulation of miR-21 by HER2/neu signaling promotes cell invasion.''; J Biol Chem, 2009 PubMed
  5. Citri A, Yarden Y; ''EGF-ERBB signalling: towards the systems level.''; Nat Rev Mol Cell Biol, 2006 PubMed
  6. McCarty JH; ''The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events.''; Bioessays, 1998 PubMed
  7. Scaltriti M, Baselga J; ''The epidermal growth factor receptor pathway: a model for targeted therapy.''; Clin Cancer Res, 2006 PubMed
  8. Marmor MD, Skaria KB, Yarden Y; ''Signal transduction and oncogenesis by ErbB/HER receptors.''; Int J Radiat Oncol Biol Phys, 2004 PubMed
  9. Olayioye MA, Neve RM, Lane HA, Hynes NE; ''The ErbB signaling network: receptor heterodimerization in development and cancer.''; EMBO J, 2000 PubMed
  10. Clark DE, Williams CC, Duplessis TT, Moring KL, Notwick AR, Long W, Lane WS, Beuvink I, Hynes NE, Jones FE; ''ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events.''; J Biol Chem, 2005 PubMed
  11. Schulze WX, Deng L, Mann M; ''Phosphotyrosine interactome of the ErbB-receptor kinase family.''; Mol Syst Biol, 2005 PubMed
  12. Liang J, Slingerland JM; ''Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.''; Cell Cycle, 2003 PubMed
  13. Muthuswamy SK, Gilman M, Brugge JS; ''Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers.''; Mol Cell Biol, 1999 PubMed
  14. Hynes NE, Lane HA; ''ERBB receptors and cancer: the complexity of targeted inhibitors.''; Nat Rev Cancer, 2005 PubMed
  15. Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS; ''Epidermal growth factor receptor (EGFR) signaling in cancer.''; Gene, 2006 PubMed
  16. Holbro T, Hynes NE; ''ErbB receptors: directing key signaling networks throughout life.''; Annu Rev Pharmacol Toxicol, 2004 PubMed
  17. Yarden Y, Sliwkowski MX; ''Untangling the ErbB signalling network.''; Nat Rev Mol Cell Biol, 2001 PubMed
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96366view 00:28, 10 March 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
94739view 08:06, 5 October 2017Mkutmonfix unconnected line
91869view 15:17, 31 March 2017KhanspersModified description
91868view 15:13, 31 March 2017Khanspersupdated phosphorylation states, interactions, metabolites, cell components etc
86901view 00:59, 14 July 2016MkutmonOntology Term : 'oxidative phosphorylation pathway' added !
86900view 00:59, 14 July 2016MkutmonOntology Term : 'PW:0000034' removed !
80202view 12:32, 22 May 2015Khanspersadded mir21 targeting of ERBB2 and MYC
69914view 12:37, 11 July 2013AlexanderPicoModified title
68012view 00:32, 29 June 2013EgonwAdded a missing metabolite identifier.
67205view 03:20, 26 June 2013Christine ChichesterOntology Term : 'epidermal growth factor/neuregulin signaling pathway' added !
63184view 13:44, 8 May 2013MaintBotUpdating gpml version
41091view 16:21, 1 March 2011MaintBotRemoved redundant pathway information and comments
38179view 21:20, 21 August 2010AlexanderPicoConverted pathway objects
38178view 21:16, 21 August 2010AlexanderPicoAdded literature references
38177view 21:10, 21 August 2010AlexanderPicoConverted pathway objects
38176view 21:01, 21 August 2010AlexanderPicoSpecify description
38175view 20:59, 21 August 2010AlexanderPicoAdded reference and more EGFR connections
38174view 20:49, 21 August 2010AlexanderPicoPeriodical save, work in progress
38173view 20:39, 21 August 2010AlexanderPicoPeriodical save, work in progress
38172view 20:28, 21 August 2010AlexanderPicoModified description
29836view 03:01, 4 June 2009UomoamareAll nodes annotated through NCBI-GeneID
29835view 02:56, 4 June 2009UomoamarePeriodical save, work in progress
29834view 02:46, 4 June 2009UomoamarePeriodical save, work in progress
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29738view 15:34, 1 June 2009KhanspersModified categories
28873view 08:02, 9 March 2009UomoamareSpecify description
28851view 03:39, 8 March 2009UomoamareSpecify description
28828view 06:45, 7 March 2009UomoamareModified description
28827view 06:40, 7 March 2009Uomoamare1 revision
28826view 06:36, 7 March 2009UomoamarePeriodical save, work in progress
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28822view 11:04, 6 March 2009UomoamareSpecify description
28821view 10:56, 6 March 2009UomoamareErbB Signaling Pathway
28820view 10:53, 6 March 2009UomoamareErbB
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28816view 09:35, 6 March 2009UomoamarePeriodical save, work in progress
28815view 09:22, 6 March 2009UomoamareERBB SIGNALING PATHWAY
28814view 09:20, 6 March 2009UomoamareSpecify description
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External references


View all...
NameTypeDatabase referenceComment
ABLGeneProduct25 (Entrez Gene)
AKT3GeneProduct10000 (Entrez Gene)
ARAFGeneProduct369 (Entrez Gene)
AREGGeneProduct374 (Entrez Gene)
ApoptosisPathwayWP254 (WikiPathways)
BADGeneProduct572 (Entrez Gene)
BIMGeneProduct10018 (Entrez Gene)
BTCGeneProduct685 (Entrez Gene)
CAMK2AGeneProduct815 (Entrez Gene)
CBLGeneProduct23624 (Entrez Gene)
CCND1GeneProduct595 (Entrez Gene)
CRKGeneProduct1398 (Entrez Gene)
Ca2+MetaboliteCHEBI:22984 (ChEBI)
Calcium Signaling PathwayPathway
Cell CyclePathwayWP179 (WikiPathways)
DiacylglycerolMetaboliteCHEBI:18035 (ChEBI)
EGFGeneProduct1950 (Entrez Gene)
ELKGeneProduct2002 (Entrez Gene)
ERBB1GeneProduct1956 (Entrez Gene)
ERBB2GeneProduct2064 (Entrez Gene)
ERBB3GeneProduct2065 (Entrez Gene)
ERBB4GeneProduct2066 (Entrez Gene)
EREGGeneProduct2069 (Entrez Gene)
ERKGeneProduct5594 (Entrez Gene)
FAKGeneProduct5747 (Entrez Gene)
FOXO1GeneProduct2308 (Entrez Gene)
GAB1GeneProduct2549 (Entrez Gene)
GRB2GeneProduct2885 (Entrez Gene)
GSK3GeneProduct2932 (Entrez Gene)
HBEGFGeneProduct1839 (Entrez Gene)
HRASGeneProduct3265 (Entrez Gene)
IP3MetaboliteCHEBI:16595 (ChEBI)
JNKGeneProduct5599 (Entrez Gene)
JUNGeneProduct3725 (Entrez Gene)
Jnkk2GeneProduct5609 (Entrez Gene)
KRASGeneProduct3845 (Entrez Gene)
MAPK Signaling PathwayPathwayWP382 (WikiPathways)
MDM2GeneProduct4193 (Entrez Gene)
MEK1GeneProduct5604 (Entrez Gene)
MIR21RnaENSG00000199004 (Ensembl)
MYCGeneProduct4609 (Entrez Gene)
MycGeneProduct4609 (Entrez Gene)
NCKGeneProduct4690 (Entrez Gene)
NRG1GeneProduct3084 (Entrez Gene)
NRG2GeneProduct9542 (Entrez Gene)
NRG3GeneProduct10718 (Entrez Gene)
NRG4GeneProduct145957 (Entrez Gene)
P70S6KGeneProduct6198 (Entrez Gene)
PAK4GeneProduct10298 (Entrez Gene)
PDK1GeneProduct5163 (Entrez Gene)
PI3KGeneProduct23533 (Entrez Gene)
PIP2MetaboliteCHEBI:18348 (ChEBI)
PIP3MetaboliteHMDB04249 (HMDB)
PLCGGeneProduct5335 (Entrez Gene)
PRKCAGeneProduct5578 (Entrez Gene)
SHCGeneProduct25759 (Entrez Gene)
SOSGeneProduct6654 (Entrez Gene)
SRCGeneProduct6714 (Entrez Gene)
STAT5GeneProduct6776 (Entrez Gene)
TGFAGeneProduct7039 (Entrez Gene)
eIF-4EBPGeneProduct1978 (Entrez Gene)
mTORGeneProduct2475 (Entrez Gene)
mTor Signaling PathwayPathway
p21GeneProduct1026 (Entrez Gene)
p27GeneProduct1027 (Entrez Gene)
p53GeneProduct7157 (Entrez Gene)

Annotated Interactions

<cite>No annotated interactions</cite>