ErbB Signaling Pathway (Homo sapiens)

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+pAdhesionMigration+p+pReceptor ubiquitylationProteinsynthesisDG+p(EGFR)Metabolism+pCellular targets+pActivation by ErbB2overexpression (cancers)SurvivalIP3+pMigration / InvasionDNA+pCellular targetsDNAGliomaER+p+p+pNon-smallcell lungcancerAdhesionNo signalingEndometrialcancerPancreaticCancerCa+2+p+pCell survival+pDifferentiation+pDNA+p+pAngiogenesis+pDegradationCell cycleprogressionColoncancer+p(HER2/Neu)DNAProliferationERBB2NCKSTAT5CCND1ABLBTCBIMARAFPI3KFAKMYCPAK4p21P70S6KEREGFOXO1JUNERBB4Cell cycle pathwayERBB4AKT3NRG3NRG1GRB2ERBB2ERBB1CRKPDK1ERBB3JNKPIP2KRASTGFAERBB2p53CAMK2AGRB2MAPK signaling pathwayNRG2ERBB4Jnkk2NRG4GSK3MEK1BADmTor signaling pathwayERBB3ERBB1PLCGPRKCAERBB2SRCHBEGFmTORCBLERBB3SHCERKPIP3GAB1p27Calcium signaling pathwaySTAT5Apoptosis pathwayERBB2AREGMycHRASeIF-4EBPERBB1MDM2EGFELKSOS1ELK


Description

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.


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Ontology Terms

 

Bibliography

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  1. 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 Europe PMC Scholia
  2. 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 Europe PMC Scholia
  3. Yarden Y, Sliwkowski MX; ''Untangling the ErbB signalling network.''; Nat Rev Mol Cell Biol, 2001 PubMed Europe PMC Scholia
  4. Scaltriti M, Baselga J; ''The epidermal growth factor receptor pathway: a model for targeted therapy.''; Clin Cancer Res, 2006 PubMed Europe PMC Scholia
  5. Holbro T, Hynes NE; ''ErbB receptors: directing key signaling networks throughout life.''; Annu Rev Pharmacol Toxicol, 2004 PubMed Europe PMC Scholia
  6. 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 Europe PMC Scholia
  7. McCarty JH; ''The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events.''; Bioessays, 1998 PubMed Europe PMC Scholia
  8. Citri A, Yarden Y; ''EGF-ERBB signalling: towards the systems level.''; Nat Rev Mol Cell Biol, 2006 PubMed Europe PMC Scholia
  9. Hynes NE, Lane HA; ''ERBB receptors and cancer: the complexity of targeted inhibitors.''; Nat Rev Cancer, 2005 PubMed Europe PMC Scholia
  10. 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 Europe PMC Scholia
  11. Olayioye MA, Neve RM, Lane HA, Hynes NE; ''The ErbB signaling network: receptor heterodimerization in development and cancer.''; EMBO J, 2000 PubMed Europe PMC Scholia
  12. Marmor MD, Skaria KB, Yarden Y; ''Signal transduction and oncogenesis by ErbB/HER receptors.''; Int J Radiat Oncol Biol Phys, 2004 PubMed Europe PMC Scholia
  13. 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 Europe PMC Scholia
  14. Oda K, Matsuoka Y, Funahashi A, Kitano H; ''A comprehensive pathway map of epidermal growth factor receptor signaling.''; Mol Syst Biol, 2005 PubMed Europe PMC Scholia
  15. 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 Europe PMC Scholia
  16. Schulze WX, Deng L, Mann M; ''Phosphotyrosine interactome of the ErbB-receptor kinase family.''; Mol Syst Biol, 2005 PubMed Europe PMC Scholia
  17. Liang J, Slingerland JM; ''Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.''; Cell Cycle, 2003 PubMed Europe PMC Scholia
  18. Zheng CF, Guan KL; ''Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues.''; EMBO J, 1994 PubMed Europe PMC Scholia
  19. Besnard A, Galan-Rodriguez B, Vanhoutte P, Caboche J; ''Elk-1 a transcription factor with multiple facets in the brain.''; Front Neurosci, 2011 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
111993view04:38, 15 September 2020KhanspersAdded lit refs for phosphosites on ELK1 and MEK
111175view04:54, 22 July 2020EgonwMade another three pathways clickable
110910view22:18, 19 June 2020Khanspersfixed unconnected interaction
108898view19:18, 5 February 2020Khanspersupdated label for EIF4EBP1
108897view19:16, 5 February 2020Khanspersadded phosphosite to eiF-4EBP
108887view23:14, 4 February 2020Khanspersupdated phosphosite
108882view19:45, 4 February 2020Khanspersupdated ligand binding
108881view19:42, 4 February 2020Khanspersupdated ERBBs as complexes
108880view19:41, 4 February 2020Khansperstest
108831view00:20, 1 February 2020Khanspersupdated interaction with PDPK1
108769view02:13, 29 January 2020Khanspersfinal touches
108765view01:32, 29 January 2020Khanspersmore phosphosites
108761view01:12, 29 January 2020Khanspersupdated to official symbols
108760view01:10, 29 January 2020Khanspersupdated xref for PDK1 (PDPK1)
108759view22:53, 28 January 2020Khanspersadded phosphosites and updated node sizing and layout
108758view19:00, 28 January 2020Khanspersadded phosphosites for MAPK8/9/10
108757view17:43, 28 January 2020Khanspersupdated MEK/ERK
108752view05:58, 28 January 2020Khanspersadded phosphosites
108751view05:29, 28 January 2020Khanspersadded phospho sites
108750view05:05, 28 January 2020Khanspersupdated phospho sites
108749view01:19, 28 January 2020KhanspersAdding phosphosites
108748view00:50, 28 January 2020Khanspersadded phosphosite
108747view22:11, 27 January 2020KhanspersAdded phospho sites
108256view14:22, 3 December 2019L DupuisConnected unconnected lines
108194view10:56, 29 November 2019FehrhartOntology Term : 'multiple sclerosis' added !
108193view10:56, 29 November 2019FehrhartOntology Term : 'Alzheimer's disease' added !
108192view10:56, 29 November 2019FehrhartOntology Term : 'cancer' added !
106821view13:30, 17 September 2019MaintBotHMDB identifier normalization
106405view21:33, 28 August 2019KhanspersModified description
105438view04:50, 8 August 2019KhanspersModified description
105003view04:54, 28 June 2019KhanspersModified description
102179view23:07, 5 December 2018Ejaehnigfurther improved alignment of nodes
102176view22:36, 5 December 2018Ejaehnigimproved alignment of nodes in groups
102175view22:18, 5 December 2018EjaehnigThis pathway was ported from KEGG, but the KEGG pathway used a single protein node for multiple genes in many cases. For these nodes, I split the node into groups containing all of the genes underlying each node in the KEGG pathway (interchangeable genes
98355view05:36, 24 August 2018EgonwUpdated the MIR21 identifier.
96366view07:28, 10 March 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
94739view15:06, 5 October 2017Mkutmonfix unconnected line
91869view22:17, 31 March 2017KhanspersModified description
91868view22:13, 31 March 2017Khanspersupdated phosphorylation states, interactions, metabolites, cell components etc
86901view07:59, 14 July 2016MkutmonOntology Term : 'oxidative phosphorylation pathway' added !
86900view07:59, 14 July 2016MkutmonOntology Term : 'PW:0000034' removed !
80202view19:32, 22 May 2015Khanspersadded mir21 targeting of ERBB2 and MYC
69914view19:37, 11 July 2013AlexanderPicoModified title
68012view07:32, 29 June 2013EgonwAdded a missing metabolite identifier.
67205view10:20, 26 June 2013Christine ChichesterOntology Term : 'epidermal growth factor/neuregulin signaling pathway' added !
63184view20:44, 8 May 2013MaintBotUpdating gpml version
41091view23:21, 1 March 2011MaintBotRemoved redundant pathway information and comments
38179view04:20, 22 August 2010AlexanderPicoConverted pathway objects
38178view04:16, 22 August 2010AlexanderPicoAdded literature references
38177view04:10, 22 August 2010AlexanderPicoConverted pathway objects

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ABLGeneProduct25 (Entrez Gene)
AKT3GeneProduct10000 (Entrez Gene)
ARAFGeneProduct369 (Entrez Gene)
AREGGeneProduct374 (Entrez Gene)
Apoptosis pathwayPathway
BADGeneProduct572 (Entrez Gene)
BIMGeneProduct10018 (Entrez Gene)
BTCGeneProduct685 (Entrez Gene)
CAMK2AGeneProduct815 (Entrez Gene)
CBLGeneProduct23624 (Entrez Gene)
CCND1GeneProduct595 (Entrez Gene)
CRKGeneProduct1398 (Entrez Gene)
Calcium signaling pathwayPathway
Cell cycle pathwayPathway
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)
JNKGeneProduct5599 (Entrez Gene)
JUNGeneProduct3725 (Entrez Gene)
Jnkk2GeneProduct5609 (Entrez Gene)
KRASGeneProduct3845 (Entrez Gene)
MAPK signaling pathwayPathway
MDM2GeneProduct4193 (Entrez Gene)
MEK1GeneProduct5604 (Entrez Gene)
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)
PIP2Metabolite
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

No annotated interactions

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