ErbB signaling pathway (Homo sapiens)

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1-3, 5-16Degradation(EGFR)Cell cycleprogression+p+pPancreaticCancer+p+p+p+pIP3(HER2/Neu)DNAEndometrialcancerColoncancerAdhesionMigration+p+p+pMigration / InvasionProliferation+pCellular targetsDG+p+p+pReceptor ubiquitylation+pActivation by ErbB2overexpression (cancers)+p+pCa+2GliomaMetabolismDNA+p+pCell survivalSurvivalNo signalingDNAAdhesionDNACellular targetsProteinsynthesisNon-smallcell lungcancerAngiogenesisDifferentiation+pERGRB2CCND1BTCJUNmTORAREGMYCFAKGSK3ERBB3mTor signaling pathwayERBB3BIMAKT3PDK1HBEGFPRKCACBLBADNRG2eIF-4EBPABLERBB4Cell cycle pathwayFOXO1ERBB1SOSHRASCRKTGFAELKNRG1MycSRCPI3KMDM2GRB2NRG4JNKp21PAK4ARAFEREGPLCGERBB4ERBB4KRASEGFp53PIP2ERBB2Jnkk2NRG3ERBB1Calcium signaling pathwayMAPK signaling pathwaySTAT5ERBB2Apoptosis pathwayNCKCAMK2Ap27ERBB2P70S6KERKMEK1SHCERBB2PIP3ERBB2STAT5GAB1ERBB3ERBB14ELK


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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Bibliography

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  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 Europe PMC Scholia
  2. Holbro T, Hynes NE; ''ErbB receptors: directing key signaling networks throughout life.''; Annu Rev Pharmacol Toxicol, 2004 PubMed Europe PMC Scholia
  3. 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
  4. Hynes NE, Lane HA; ''ERBB receptors and cancer: the complexity of targeted inhibitors.''; Nat Rev Cancer, 2005 PubMed Europe PMC Scholia
  5. 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
  6. 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
  7. 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
  8. McCarty JH; ''The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events.''; Bioessays, 1998 PubMed Europe PMC Scholia
  9. Liang J, Slingerland JM; ''Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.''; Cell Cycle, 2003 PubMed Europe PMC Scholia
  10. Yarden Y, Sliwkowski MX; ''Untangling the ErbB signalling network.''; Nat Rev Mol Cell Biol, 2001 PubMed Europe PMC Scholia
  11. 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
  12. 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
  13. 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
  14. Scaltriti M, Baselga J; ''The epidermal growth factor receptor pathway: a model for targeted therapy.''; Clin Cancer Res, 2006 PubMed Europe PMC Scholia
  15. Schulze WX, Deng L, Mann M; ''Phosphotyrosine interactome of the ErbB-receptor kinase family.''; Mol Syst Biol, 2005 PubMed Europe PMC Scholia
  16. 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
  17. Citri A, Yarden Y; ''EGF-ERBB signalling: towards the systems level.''; Nat Rev Mol Cell Biol, 2006 PubMed Europe PMC Scholia
  18. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E; ''PhosphoSitePlus, 2014: mutations, PTMs and recalibrations.''; Nucleic Acids Res, 2015 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
127753view11:42, 2 December 2023EgonwChEBI id for Ca2+ instead of the "Ca" atom
127240view00:19, 26 August 2023KhanspersAdded lit ref and updated description
126227view06:25, 17 April 2023EgonwLicense is CCZero
118930view17:21, 4 June 2021Finterlyspelling parentsybol corrected to parent symbol for state comment
116519view11:00, 7 May 2021EweitzModified title
112158view18:14, 29 September 2020Khanspersfixed ptm state comments
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.

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 pathwayPathwayhsa04020 (KEGG Pathway)
Cell cycle pathwayPathwayhsa04110 (KEGG Pathway)
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 pathwayPathwayhsa04010 (KEGG Pathway)
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 pathwayPathwayhsa04150 (KEGG Pathway)
p21GeneProduct1026 (Entrez Gene)
p27GeneProduct1027 (Entrez Gene)
p53GeneProduct7157 (Entrez Gene)

Annotated Interactions

No annotated interactions

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