The ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including proliferation, differentiation, cell motility, and survival. Ligand binding to the four closely related members of this RTK family -epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues (pY) within the cytoplasmic tail. Signaling effectors containing binding pockets for pY-containing peptides are recruited to activated receptors and induce the various signaling pathways. The Shc- and/or Grb2-activated mitogen-activated protein kinase (MAPK) pathway is a common target downstream of all ErbB receptors. Similarly, the phosphatidylinositol-3-kinase (PI-3K) pathway is directly or indirectly activated by most ErbBs. Several cytoplasmic docking proteins appear to be recruited by specific ErbB receptors and less exploited by others. These include the adaptors Crk, Nck, the phospholipase C gamma (PLCgamma), the intracellular tyrosine kinase Src, or the Cbl E3 ubiquitin protein ligase.

Environmental Information Processing; Signal transduction
BRITE hierarchy

Rhinopithecus roxellana (golden snub-nosed monkey) [GN:rro]

PMID:14967450

Marmor MD, Skaria KB, Yarden Y.

Signal transduction and oncogenesis by ErbB/HER receptors.

Int J Radiat Oncol Biol Phys 58:903-13 (2004)
DOI:10.1016/j.ijrobp.2003.06.002

PMID:11252954

Yarden Y, Sliwkowski MX.

Untangling the ErbB signalling network.

Nat Rev Mol Cell Biol 2:127-37 (2001)
DOI:10.1038/35052073

PMID:16829981

Citri A, Yarden Y.

EGF-ERBB signalling: towards the systems level.

Nat Rev Mol Cell Biol 7:505-16 (2006)
DOI:10.1038/nrm1962

PMID:17000658

Scaltriti M, Baselga J.

The epidermal growth factor receptor pathway: a model for targeted therapy.

Clin Cancer Res 12:5268-72 (2006)
DOI:10.1158/1078-0432.CCR-05-1554

PMID:16377102

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 366:2-16 (2006)
DOI:10.1016/j.gene.2005.10.018

PMID:14744244

Holbro T, Hynes NE.

ErbB receptors: directing key signaling networks throughout life.

Annu Rev Pharmacol Toxicol 44:195-217 (2004)
DOI:10.1146/annurev.pharmtox.44.101802.121440

PMID:12851486

Liang J, Slingerland JM.

Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.

Cell Cycle 2:339-45 (2003)
DOI:10.4161/cc.2.4.433

PMID:15864276

Hynes NE, Lane HA.

ERBB receptors and cancer: the complexity of targeted inhibitors.

Nat Rev Cancer 5:341-54 (2005)
DOI:10.1038/nrc1609

PMID:16729045

Oda K, Matsuoka Y, Funahashi A, Kitano H.

A comprehensive pathway map of epidermal growth factor receptor signaling.

Mol Syst Biol 1:2005.0010 (2005)
DOI:10.1038/msb4100014

PMID:16729043

Schulze WX, Deng L, Mann M.

Phosphotyrosine interactome of the ErbB-receptor kinase family.

Mol Syst Biol 1:2005.0008 (2005)
DOI:10.1038/msb4100012

PMID:10880430

Olayioye MA, Neve RM, Lane HA, Hynes NE.

The ErbB signaling network: receptor heterodimerization in development and cancer.

EMBO J 19:3159-67 (2000)
DOI:10.1093/emboj/19.13.3159

PMID:9872057

McCarty JH.

The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events.

Bioessays 20:913-21 (1998)
DOI:10.1002/(SICI)1521-1878(199811)20:11<913::AID-BIES6>3.0.CO;2-T

PMID:15863494

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 280:24175-80 (2005)
DOI:10.1074/jbc.M414044200

PMID:10490623

Muthuswamy SK, Gilman M, Brugge JS.

Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers.

Mol Cell Biol 19:6845-57 (1999)
DOI:10.1128/MCB.19.10.6845

PMID:9642287

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 273:17186-91 (1998)
DOI:10.1074/jbc.273.27.17186