Gene Symbol: erbB3
Description: erb-b2 receptor tyrosine kinase 3
Alias: ErbB-3, HER3, LCCS2, MDA-BF-1, c-erbB-3, c-erbB3, erbB3-S, p180-ErbB3, p45-sErbB3, p85-sErbB3, receptor tyrosine-protein kinase erbB-3, human epidermal growth factor receptor 3, proto-oncogene-like protein c-ErbB-3, tyrosine kinase-type cell surface receptor HER3, v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3
Species: human
Products:     erbB3

Top Publications

  1. Choi B, Cai X, Yuan B, Huang Z, Fan X, Deng H, et al. HER3 intracellular domains play a crucial role in HER3/HER2 dimerization and activation of downstream signaling pathways. Protein Cell. 2012;3:781-9 pubmed publisher
    ..Unlike other members in the family, the kinase domain of HER3 lacks key amino acid residues for catalytic activity...
  2. Kraus M, Issing W, Miki T, Popescu N, Aaronson S. Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. Proc Natl Acad Sci U S A. 1989;86:9193-7 pubmed
    ..with structural features identifying it as a member of the ERBB gene family, prompting us to designate the gene as ERBB3. It was mapped to human chromosome 12q13 and was shown to be expressed as a 6...
  3. Garrett J, Olivares M, Rinehart C, Granja Ingram N, Sanchez V, Chakrabarty A, et al. Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase. Proc Natl Acad Sci U S A. 2011;108:5021-6 pubmed publisher
    Sustained and complete inhibition of HER3 and its output to PI3K/Akt are required for the optimal antitumor effect of therapeutic inhibitors of the HER2 oncogene...
  4. Jaiswal B, Kljavin N, Stawiski E, Chan E, Parikh C, Durinck S, et al. Oncogenic ERBB3 mutations in human cancers. Cancer Cell. 2013;23:603-17 pubmed publisher
    ..b>ERBB3/HER3, the only member with an impaired kinase domain, although amplified or overexpressed in some cancers, has not ..
  5. Sun M, Behrens C, Feng L, Ozburn N, Tang X, Yin G, et al. HER family receptor abnormalities in lung cancer brain metastases and corresponding primary tumors. Clin Cancer Res. 2009;15:4829-37 pubmed publisher
    ..for the immunohistochemical expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Her2, Her3, and phosphorylated Her3, and their ligands EGF, transforming growth factor-alpha, amphiregulin, epiregulin, ..
  6. Cho H, Leahy D. Structure of the extracellular region of HER3 reveals an interdomain tether. Science. 2002;297:1330-3 pubmed
    We have determined the 2.6 angstrom crystal structure of the entire extracellular region of human HER3 (ErbB3), a member of the epidermal growth factor receptor (EGFR) family...
  7. Yonezawa M, Wada K, Tatsuguchi A, Akamatsu T, Gudis K, Seo T, et al. Heregulin-induced VEGF expression via the ErbB3 signaling pathway in colon cancer. Digestion. 2009;80:215-25 pubmed publisher
    Heregulin (HRG/NRG) ligation to erbB3/4 promotes their respective heterodimerization with erbB2, and consequent erbB2 tyrosine phosphorylation...
  8. Todd J, Walker N, Cooper J, Smyth D, Downes K, Plagnol V, et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet. 2007;39:857-64 pubmed
    ..Several regions, including 18q22 and 18p11, showed association with autoimmune thyroid disease. This study increases the number of T1D loci with compelling evidence from six to at least ten. ..
  9. Fry W, Simion C, Sweeney C, Carraway K. Quantity control of the ErbB3 receptor tyrosine kinase at the endoplasmic reticulum. Mol Cell Biol. 2011;31:3009-18 pubmed publisher
    The ErbB3 receptor tyrosine kinase contributes to a variety of developmental processes, and its overexpression and aberrant activation promote tumor progression and therapeutic resistance...

More Information


  1. Chen L, Siddiqui S, Bose S, Mooso B, Asuncion A, Bedolla R, et al. Nrdp1-mediated regulation of ErbB3 expression by the androgen receptor in androgen-dependent but not castrate-resistant prostate cancer cells. Cancer Res. 2010;70:5994-6003 pubmed publisher
    ..Here, we show that AW can promote CRPC development by increasing the levels of the receptor tyrosine kinase ErbB3 in androgen-dependent PCa, resulting in AW-resistant cell cycle progression and increased androgen receptor (AR) ..
  2. Zhang Y, Opresko L, Shankaran H, Chrisler W, Wiley H, Resat H. HER/ErbB receptor interactions and signaling patterns in human mammary epithelial cells. BMC Cell Biol. 2009;10:78 pubmed publisher
    ..we created a clone library of human mammary epithelial (HME) cells that expresses different levels of HER2 and HER3 receptors in combination with endogenous EGFR/HER1...
  3. Scaltriti M, Verma C, Guzman M, Jimenez J, Parra J, Pedersen K, et al. Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene. 2009;28:803-14 pubmed publisher
    ..cell surface also results in the stabilization of inactive HER2 homo- (HER2/HER2) and hetero- (HER2/EGFR and HER2/HER3) dimers...
  4. Wallasch C, Weiss F, Niederfellner G, Jallal B, Issing W, Ullrich A. Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3. EMBO J. 1995;14:4267-75 pubmed
    Amplification and/or overexpression of HER2/neu and HER3 genes have been implicated in the development of cancer in humans...
  5. Lee Hoeflich S, Crocker L, Yao E, Pham T, Munroe X, Hoeflich K, et al. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res. 2008;68:5878-87 pubmed publisher
    Epidermal growth factor receptor (EGFR) and HER3 each form heterodimers with HER2 and have independently been implicated as key coreceptors that drive HER2-amplified breast cancer...
  6. Sakai K, Yokote H, Murakami Murofushi K, Tamura T, Saijo N, Nishio K. Pertuzumab, a novel HER dimerization inhibitor, inhibits the growth of human lung cancer cells mediated by the HER3 signaling pathway. Cancer Sci. 2007;98:1498-503 pubmed
    ..A lung cancer 11_18 cell line expressed a large amount of HER2 and HER3, and its cell growth was stimulated by an HER3 ligand, heregulin (HRG)-alpha...
  7. Sheng Q, Liu X, Fleming E, Yuan K, Piao H, Chen J, et al. An activated ErbB3/NRG1 autocrine loop supports in vivo proliferation in ovarian cancer cells. Cancer Cell. 2010;17:298-310 pubmed publisher
    ..ovarian cancer cell lines by RNAi, we found that an autocrine signal-transducing loop involving NRG1 and activated ErbB3 operates in a subset of primary ovarian cancers and ovarian cancer cell lines...
  8. Larsen M, Bjerre K, Lykkesfeldt A, Giobbie Hurder A, Laenkholm A, Henriksen K, et al. Activated HER-receptors in predicting outcome of ER-positive breast cancer patients treated with adjuvant endocrine therapy. Breast. 2012;21:662-8 pubmed publisher
    ..Except for HER2, which was associated with poor prognosis, none of the remaining markers were associated with DFS. However, frequent co-expression indicates a role of the other HER-family members in activation of HER2. ..
  9. Lee Y, Cho S, Seo J, Shin B, Kim H, Kim I, et al. Correlated expression of erbB-3 with hormone receptor expression and favorable clinical outcome in invasive ductal carcinomas of the breast. Am J Clin Pathol. 2007;128:1041-9 pubmed
    ..In an era of personalized targeted therapy, erbB-3 expression and its coexpressive pattern with other EGFR family members could be an important determinant for therapeutic plans for breast cancer treatment. ..
  10. Waterman H, Alroy I, Strano S, Seger R, Yarden Y. The C-terminus of the kinase-defective neuregulin receptor ErbB-3 confers mitogenic superiority and dictates endocytic routing. EMBO J. 1999;18:3348-58 pubmed
  11. McDonagh C, Huhalov A, Harms B, Adams S, Paragas V, Oyama S, et al. Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3. Mol Cancer Ther. 2012;11:582-93 pubmed publisher
    ..Activation of ErbB3, the preferred dimerization partner of ErbB2, plays a key role in driving ErbB2-amplified tumor growth, but we ..
  12. Wei Q, Chen L, Sheng L, Nordgren H, Wester K, Carlsson J. EGFR, HER2 and HER3 expression in esophageal primary tumours and corresponding metastases. Int J Oncol. 2007;31:493-9 pubmed
    The expression of EGFR, HER2 and HER3 receptors were analyzed in immunohistochemical preparations from primary esophageal tumours and corresponding lymph node metastases...
  13. Lee H, Lee H, Chin H, Kim K, Lee D. ERBB3 knockdown induces cell cycle arrest and activation of Bak and Bax-dependent apoptosis in colon cancer cells. Oncotarget. 2014;5:5138-52 pubmed
    b>ERBB3 is an emerging target for cancer therapy among the EGFR family...
  14. Holbro T, Beerli R, Maurer F, Koziczak M, Barbas C, Hynes N. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci U S A. 2003;100:8933-8 pubmed
    ..Intriguingly, loss of ErbB2 signaling is accompanied by a decrease in the phosphotyrosine content of ErbB3. On the basis of these results, it has been proposed that ErbB3 might be a partner for ErbB2 in promoting cellular ..
  15. Suenaga A, Takada N, Hatakeyama M, Ichikawa M, Yu X, Tomii K, et al. Novel mechanism of interaction of p85 subunit of phosphatidylinositol 3-kinase and ErbB3 receptor-derived phosphotyrosyl peptides. J Biol Chem. 2005;280:1321-6 pubmed
    Ligand-activated and tyrosine-phosphorylated ErbB3 receptor binds to the SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase and initiates intracellular signaling...
  16. Zhou H, Liu L, Lee K, Qin X, Grasso A, Kung H, et al. Lung tumorigenesis associated with erb-B-2 and erb-B-3 overexpression in human erb-B-3 transgenic mice is enhanced by methylnitrosourea. Oncogene. 2002;21:8732-40 pubmed
    ..This erb-B-3 mouse lung cancer model will help dissect genetic changes in lung tumorigenesis and may be useful for chemoprevention studies. ..
  17. Begnami M, Fukuda E, Fregnani J, Nonogaki S, Montagnini A, da Costa W, et al. Prognostic implications of altered human epidermal growth factor receptors (HERs) in gastric carcinomas: HER2 and HER3 are predictors of poor outcome. J Clin Oncol. 2011;29:3030-6 pubmed publisher
    ..human epidermal growth factor receptor (HER) family consists of four members: ErbB-1 (HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)...
  18. Li Z, Szabolcs M, Terwilliger J, Efstratiadis A. Prostatic intraepithelial neoplasia and adenocarcinoma in mice expressing a probasin-Neu oncogenic transgene. Carcinogenesis. 2006;27:1054-67 pubmed
    ..PIN and CAP, led to the identification of some novel biomarkers and also revealed increased expression of Egfr, Erbb3 and phosphorylated androgen receptor...
  19. Hakonarson H, Qu H, Bradfield J, Marchand L, Kim C, Glessner J, et al. A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study. Diabetes. 2008;57:1143-6 pubmed publisher
    ..These two loci are identical to two loci identified by the whole-genome association study of the Wellcome Trust Case-Control Consortium, a parallel independent discovery that adds further support to the validity of the GWA approach. ..
  20. Zhu C, Domann F. Dominant negative interference of transcription factor AP-2 causes inhibition of ErbB-3 expression and suppresses malignant cell growth. Breast Cancer Res Treat. 2002;71:47-57 pubmed
    ErbB-3 (HER3) is a member of the epidermal growth factor receptor family. Increasing evidence suggests that elevated expression of ErbB-3 is important for malignancy...
  21. Spears M, Taylor K, Munro A, Cunningham C, Mallon E, Twelves C, et al. In situ detection of HER2:HER2 and HER2:HER3 protein-protein interactions demonstrates prognostic significance in early breast cancer. Breast Cancer Res Treat. 2012;132:463-70 pubmed publisher
    HER2 overexpression/amplification is linked with poor prognosis in early breast cancer. Co-expression of HER2 and HER3 is associated with endocrine and chemotherapy resistance, driven not simply by expression but by signalling via HER2:..
  22. Berger M, Mendrola J, Lemmon M. ErbB3/HER3 does not homodimerize upon neuregulin binding at the cell surface. FEBS Lett. 2004;569:332-6 pubmed
    To understand signaling by the neuregulin (NRG) receptor ErbB3/HER3, it is important to know whether ErbB3 forms homodimers upon ligand binding...
  23. Chaib H, Cockrell E, Rubin M, Macoska J. Profiling and verification of gene expression patterns in normal and malignant human prostate tissues by cDNA microarray analysis. Neoplasia. 2001;3:43-52 pubmed
    ..for 8 of 15 genes have been reported previously in prostate tissues (TGFbeta3, TGFBR3, IGFII, IGFBP2, VEGF, FGF7, ERBB3, MYC), but those of seven genes are reported here for the first time (MLH1, CYP1B1, RFC4, EPHB3, MGST1, BTEB2, MLP)..
  24. Yang S, Raymond Stintz M, Ying W, Zhang J, Lidke D, Steinberg S, et al. Mapping ErbB receptors on breast cancer cell membranes during signal transduction. J Cell Sci. 2007;120:2763-73 pubmed
    ..Heregulin leads to dramatic clusters of ErbB3 that contain some ErbB2 and EGFR and abundant PI 3-kinase...
  25. Diamonti A, Guy P, Ivanof C, Wong K, Sweeney C, Carraway K. An RBCC protein implicated in maintenance of steady-state neuregulin receptor levels. Proc Natl Acad Sci U S A. 2002;99:2866-71 pubmed
    ..In a screen for proteins that might regulate the trafficking or localization of the ErbB3 receptor, we have identified a tripartite or RBCC (RING, B-box, coiled-coil) protein that interacts with the ..
  26. Funes M, Miller J, Lai C, Carraway K, Sweeney C. The mucin Muc4 potentiates neuregulin signaling by increasing the cell-surface populations of ErbB2 and ErbB3. J Biol Chem. 2006;281:19310-9 pubmed
    ..experiments and immunofluorescence studies suggest that Muc4 induces the relocalization of the ErbB2 and ErbB3 receptors from intracellular compartments to the plasma membrane...
  27. Carraway K, Sliwkowski M, Akita R, Platko J, Guy P, Nuijens A, et al. The erbB3 gene product is a receptor for heregulin. J Biol Chem. 1994;269:14303-6 pubmed
    b>ErbB3 is a member of the epidermal growth factor (EGF) receptor subfamily of receptor tyrosine kinases and is believed to be a receptor for an unknown ligand...
  28. Xia W, Liu L, Ho P, Spector N. Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016. Oncogene. 2004;23:646-53 pubmed
    ..Furthermore, phospho-p95ErbB2 forms heterodimers with ErbB3, but not EGFR, while p185ErbB2 heterodimerizes with both EGFR and ErbB3...
  29. Gur G, Rubin C, Katz M, Amit I, Citri A, Nilsson J, et al. LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation. EMBO J. 2004;23:3270-81 pubmed
    ..We conclude that LRIG1 evolved in mammals as a feedback negative attenuator of signaling by receptor tyrosine kinases. ..
  30. Yoo J, Wang X, Rishi A, Lessor T, Xia X, Gustafson T, et al. Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of this binding by heregulin. Br J Cancer. 2000;82:683-90 pubmed
    ..Ebp1 translocated from the cytoplasm into the nucleus following heregulin stimulation. These findings suggest that Ebp1 may be a downstream member of an ErbB-3-regulated signal transduction pathway. ..
  31. Sliwkowski M, Schaefer G, Akita R, Lofgren J, Fitzpatrick V, Nuijens A, et al. Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. J Biol Chem. 1994;269:14661-5 pubmed
    ..Cells that are transfected with the closely related receptor, erbB3, display a single class of lower affinity heregulin binding sites than has been previously observed on breast ..
  32. Huang X, Gao L, Wang S, McManaman J, Thor A, Yang X, et al. Heterotrimerization of the growth factor receptors erbB2, erbB3, and insulin-like growth factor-i receptor in breast cancer cells resistant to herceptin. Cancer Res. 2010;70:1204-14 pubmed publisher
    ..we report enhanced activation of downstream signaling pathways emanating from the growth factor receptors erbB2, erbB3, and insulin-like growth factor-I receptor (IGF-IR) in trastuzumab-resistant breast cancer cells...
  33. Fernandes A, Hamburger A, Gerwin B. Dominance of ErbB-1 heterodimers in lung epithelial cells overexpressing ErbB-2. Both ErbB-1 and ErbB-2 contribute significantly to tumorigenicity. Am J Respir Cell Mol Biol. 1999;21:701-9 pubmed
    ..This work further suggests that ErbB-3 and -4 species may also contribute to tumorigenic conversion and that their expression levels may be increased by signaling initiated by TGF-alpha. ..
  34. Xia X, Lessor T, Zhang Y, Woodford N, Hamburger A. Analysis of the expression pattern of Ebp1, an ErbB-3-binding protein. Biochem Biophys Res Commun. 2001;289:240-4 pubmed
    ..5 kDa. The molecular mass of endogenous Ebp1 protein derived from mouse liver and brain was determined by mass spectrometry and the data confirm that translation of endogenous Ebp1 in tissues is initiated from the second in-frame ATG. ..
  35. Dawson J, Bu Z, Lemmon M. Ligand-induced structural transitions in ErbB receptor extracellular domains. Structure. 2007;15:942-54 pubmed
    ..directly the transition from a tethered to extended configuration in the monomeric extracellular regions of ErbB3 and a dimerization-defective EGFR mutant...
  36. Lee H, Akita R, Sliwkowski M, Maihle N. A naturally occurring secreted human ErbB3 receptor isoform inhibits heregulin-stimulated activation of ErbB2, ErbB3, and ErbB4. Cancer Res. 2001;61:4467-73 pubmed
    ..In this study, we demonstrate that a naturally occurring secreted form of the human ErbB3 receptor, p85-soluble ErbB3 (sErbB3), is a potent negative regulator of heregulin (HRG)-stimulated ErbB2, ErbB3, ..
  37. Junttila T, Akita R, Parsons K, Fields C, Lewis Phillips G, Friedman L, et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell. 2009;15:429-40 pubmed publisher
    ..Here, we describe a mechanism of action for trastuzumab whereby antibody treatment disrupts ligand-independent HER2/HER3 interactions in HER2-amplified cells...
  38. Reschke M, Mihic Probst D, van der Horst E, Knyazev P, Wild P, Hutterer M, et al. HER3 is a determinant for poor prognosis in melanoma. Clin Cancer Res. 2008;14:5188-97 pubmed publisher
    The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in breast, lung, and ovarian cancer...
  39. Park E, Baron R, Landgraf R. Higher-order association states of cellular ERBB3 probed with photo-cross-linkable aptamers. Biochemistry. 2008;47:11992-2005 pubmed publisher
    ..we converted a previously selected, inhibitory aptamer that binds the soluble extracellular domains of the ERBB3 receptor into a targeted and highly specific cross-linking reagent in a live cell setting...
  40. Koutras A, Kalogeras K, Dimopoulos M, Wirtz R, Dafni U, Briasoulis E, et al. Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) study. Br J Cancer. 2008;99:1775-85 pubmed publisher
    ..b>HER3 and HER4 mRNA level had a favourable prognostic value in terms of OS and disease-free survival (DFS), respectively...
  41. Hayashi M, Inokuchi M, Takagi Y, Yamada H, Kojima K, Kumagai J, et al. High expression of HER3 is associated with a decreased survival in gastric cancer. Clin Cancer Res. 2008;14:7843-9 pubmed publisher
    ..A multivariate analysis was done with the overall survival. HER3 expression was significantly associated with parameters involved with tumor progression, including the depth of ..
  42. Aurisicchio L, Marra E, Luberto L, Carlomosti F, De Vitis C, Noto A, et al. Novel anti-ErbB3 monoclonal antibodies show therapeutic efficacy in xenografted and spontaneous mouse tumors. J Cell Physiol. 2012;227:3381-8 pubmed publisher
    The role of the ErbB3 receptor in signal transduction is to augment the signaling repertoire of active heterodimeric ErbB receptor complexes through activating the PI3K/AKT pathway, which in turn promotes survival and proliferation...
  43. Alimandi M, Romano A, Curia M, Muraro R, Fedi P, Aaronson S, et al. Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene. 1995;10:1813-21 pubmed
    ..Furthermore, at high expression levels of ErbB2 which cause transformation, ErbB3 enhanced focus formation by one order of magnitude...
  44. Crovello C, Lai C, Cantley L, Carraway K. Differential signaling by the epidermal growth factor-like growth factors neuregulin-1 and neuregulin-2. J Biol Chem. 1998;273:26954-61 pubmed
    ..Although neuregulin-1 and neuregulin-2 are both binding ligands for the ErbB3 and ErbB4 receptors, they exhibit distinct biological activities depending on cellular context...
  45. Liles J, Arnoletti J, Tzeng C, Howard J, Kossenkov A, Kulesza P, et al. ErbB3 expression promotes tumorigenesis in pancreatic adenocarcinoma. Cancer Biol Ther. 2010;10:555-63 pubmed
    Historically, ErbB3 has been overlooked within the ErbB receptor family due to its perceived lack of tyrosine kinase activity...
  46. Gijsen M, King P, Perera T, Parker P, Harris A, Larijani B, et al. HER2 phosphorylation is maintained by a PKB negative feedback loop in response to anti-HER2 herceptin in breast cancer. PLoS Biol. 2010;8:e1000563 pubmed publisher
    ..We also investigated the effects of acute and chronic Herceptin treatment on HER3 and PKB phosphorylation in HER2-positive breast cancer cells...
  47. Izycka Swieszewska E, Wozniak A, Drozynska E, Kot J, Grajkowska W, Klepacka T, et al. Expression and significance of HER family receptors in neuroblastic tumors. Clin Exp Metastasis. 2011;28:271-82 pubmed publisher
    ..Our study showed that the role of HER family members in NT biology is interrelated and complex but their expression level may present a novel prognostic factor for NT patients outcome. ..
  48. Tao J, Castel P, Radosevic Robin N, Elkabets M, Auricchio N, Aceto N, et al. Antagonism of EGFR and HER3 enhances the response to inhibitors of the PI3K-Akt pathway in triple-negative breast cancer. Sci Signal. 2014;7:ra29 pubmed publisher
    ..However, activation of another EGFR family member [human epidermal growth factor receptor 3 (HER3) (or ErbB3)] may limit the antitumor effects of these drugs...
  49. Awata T, Kawasaki E, Tanaka S, Ikegami H, Maruyama T, Shimada A, et al. Association of type 1 diabetes with two Loci on 12q13 and 16p13 and the influence coexisting thyroid autoimmunity in Japanese. J Clin Endocrinol Metab. 2009;94:231-5 pubmed publisher
    ..Two single-nucleotide polymorphisms (SNPs), rs2292399 in ERBB3 on 12q13 and rs2903692 in CLEC16A (or KIAA0350) on 16p13, were analyzed in Japanese subjects consisting of 735 T1D ..
  50. Junttila T, Laato M, Vahlberg T, Söderström K, Visakorpi T, Isola J, et al. Identification of patients with transitional cell carcinoma of the bladder overexpressing ErbB2, ErbB3, or specific ErbB4 isoforms: real-time reverse transcription-PCR analysis in estimation of ErbB receptor status from cancer patients. Clin Cancer Res. 2003;9:5346-57 pubmed
    ..Determination of cutoff expression levels indicated tumor-specific overexpression of ErbB2, ErbB3, and specific ErbB4 isoforms in a subset of TCC patients...
  51. Singer E, Landgraf R, Horan T, Slamon D, Eisenberg D. Identification of a heregulin binding site in HER3 extracellular domain. J Biol Chem. 2001;276:44266-74 pubmed
    b>HER3 (also known as c-Erb-b3) is a type I receptor tyrosine kinase similar in sequence to the epidermal growth factor (EGF) receptor. The extracellular segment of this transmembrane receptor contains four domains...
  52. Wei Q, Sheng L, Shui Y, Hu Q, Nordgren H, Carlsson J. EGFR, HER2, and HER3 expression in laryngeal primary tumors and corresponding metastases. Ann Surg Oncol. 2008;15:1193-201 pubmed publisher
    ..Expression of EGFR, HER2, and HER3 was investigated immunohistochemically in both lymph node metastases and corresponding primary laryngeal squamous ..
  53. Plowman G, Whitney G, Neubauer M, Green J, McDonald V, Todaro G, et al. Molecular cloning and expression of an additional epidermal growth factor receptor-related gene. Proc Natl Acad Sci U S A. 1990;87:4905-9 pubmed
    ..of another member of the human EGF receptor (HER) family of receptor tyrosine kinases, which we have named "HER3/ERRB3...
  54. Cooper J, Smyth D, Smiles A, Plagnol V, Walker N, Allen J, et al. Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. Nat Genet. 2008;40:1399-401 pubmed publisher
    ..7 x 10(-12)), 10p15 (PRKCQ, P = 3.7 x 10(-9)), 15q24 (CTSH, P = 3.2 x 10(-15)) and 22q13 (C1QTNF6, P = 2.0 x 10(-8)). ..
  55. Mirschberger C, Schiller C, Schräml M, Dimoudis N, Friess T, Gerdes C, et al. RG7116, a therapeutic antibody that binds the inactive HER3 receptor and is optimized for immune effector activation. Cancer Res. 2013;73:5183-94 pubmed publisher
    The EGF receptor (EGFR) HER3 is emerging as an attractive cancer therapeutic target due to its central position in the HER receptor signaling network...
  56. Kani K, Warren C, Kaddis C, Loo J, Landgraf R. Oligomers of ERBB3 have two distinct interfaces that differ in their sensitivity to disruption by heregulin. J Biol Chem. 2005;280:8238-47 pubmed
    ..The kinase-deficient ErbB3 as well as its extracellular domains are particularly prone to ligand-independent oligomerization, and oligomers ..
  57. Sithanandam G, Fornwald L, Fields J, Anderson L. Inactivation of ErbB3 by siRNA promotes apoptosis and attenuates growth and invasiveness of human lung adenocarcinoma cell line A549. Oncogene. 2005;24:1847-59 pubmed
    The ErbB3 receptor and the downstream signaling kinase Akt are implicated in proliferation of lung adenocarcinoma cells...
  58. Andrique L, Fauvin D, El Maassarani M, Colasson H, Vannier B, Seite P. ErbB3(80 kDa), a nuclear variant of the ErbB3 receptor, binds to the Cyclin D1 promoter to activate cell proliferation but is negatively controlled by p14ARF. Cell Signal. 2012;24:1074-85 pubmed publisher
    ..We report here the characterization of a nuclear variant of the kinase-defective ErbB3 receptor, ErbB3(80 kDa), spanning the intracytoplasmic domain of the receptor...
  59. Vijapurkar U, Cheng K, Koland J. Mutation of a Shc binding site tyrosine residue in ErbB3/HER3 blocks heregulin-dependent activation of mitogen-activated protein kinase. J Biol Chem. 1998;273:20996-1002 pubmed
    The ErbB2 and ErbB3 proteins together constitute a functional coreceptor for heregulin (neuregulin)...
  60. Engelman J, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park J, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039-43 pubmed
    ..We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors...
  61. Ingalla E, Miller J, Wald J, Workman H, Kaur R, Yen L, et al. Post-transcriptional mechanisms contribute to the suppression of the ErbB3 negative regulator protein Nrdp1 in mammary tumors. J Biol Chem. 2010;285:28691-7 pubmed publisher
    The ErbB2 and ErbB3 receptor tyrosine kinases act synergistically to promote cellular properties associated with tumor development...
  62. Smyth D, Plagnol V, Walker N, Cooper J, Downes K, Yang J, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med. 2008;359:2767-77 pubmed publisher
    ..These data suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases. ..
  63. Folgiero V, Avetrani P, Bon G, Di Carlo S, Fabi A, Nisticò C, et al. Induction of ErbB-3 expression by alpha6beta4 integrin contributes to tamoxifen resistance in ERbeta1-negative breast carcinomas. PLoS ONE. 2008;3:e1592 pubmed publisher
  64. Hellyer N, Kim M, Koland J. Heregulin-dependent activation of phosphoinositide 3-kinase and Akt via the ErbB2/ErbB3 co-receptor. J Biol Chem. 2001;276:42153-61 pubmed
    The ErbB2/ErbB3 heregulin co-receptor has been shown to couple to phosphoinositide (PI) 3-kinase in a heregulin-dependent manner...
  65. Ghayad S, Vendrell J, Ben Larbi S, Dumontet C, Bieche I, Cohen P. Endocrine resistance associated with activated ErbB system in breast cancer cells is reversed by inhibiting MAPK or PI3K/Akt signaling pathways. Int J Cancer. 2010;126:545-62 pubmed publisher
    ..Aberrant expression and activation of the ErbB system (phospho-EGFR, phospho-ErbB2, phospho-ErbB3, over-expression of ErbB4 and over-expression of several ErbB ligands) were also observed in the two resistant ..
  66. Wang S, Xiang B, Guix M, Olivares M, Parker J, Chung C, et al. Transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab. Mol Cell Biol. 2008;28:5605-20 pubmed publisher
    ..In turn, these ligands enhanced the association of p85 with ErbB3 and activated PI3K/Akt...
  67. Minami A, Shimono Y, Mizutani K, Nobutani K, Momose K, Azuma T, et al. Reduction of the ST6 ?-galactosamide ?-2,6-sialyltransferase 1 (ST6GAL1)-catalyzed sialylation of nectin-like molecule 2/cell adhesion molecule 1 and enhancement of ErbB2/ErbB3 signaling by microRNA-199a. J Biol Chem. 2013;288:11845-53 pubmed publisher
    ..We previously showed that Necl-2 interacts in cis with ErbB3 and suppresses the heregulin (HRG)-induced ErbB2/ErbB3 signaling for cell movement and death...
  68. Park J, Sarode V, Euhus D, Kittler R, Scherer P. Neuregulin 1-HER axis as a key mediator of hyperglycemic memory effects in breast cancer. Proc Natl Acad Sci U S A. 2012;109:21058-63 pubmed publisher
    ..mRNA expression profiling revealed that the neuregulin-1 gene, encoding an established endogenous ligand for the HER3 receptor, is activated through a putative distal enhancer...
  69. Lin S, Lee Y, Choueiri M, Wen S, Mathew P, Ye X, et al. Soluble ErbB3 levels in bone marrow and plasma of men with prostate cancer. Clin Cancer Res. 2008;14:3729-36 pubmed publisher
    Prostate cancer tends to metastasize to bone and induce osteoblastic lesions. We identified a soluble form of ErbB3 (sErbB3), p45-sErbB3, in bone marrow supernatant from men with prostate cancer bone metastasis and showed that p45-sErbB3 ..
  70. Balz L, Bartkowiak K, Andreas A, Pantel K, Niggemann B, Zanker K, et al. The interplay of HER2/HER3/PI3K and EGFR/HER2/PLC-?1 signalling in breast cancer cell migration and dissemination. J Pathol. 2012;227:234-44 pubmed publisher
    HER2 signalling by heterodimerisation with EGFR and HER3 in breast cancer is associated with worst outcome of the afflicted patients, which is attributed not only to the aggressiveness of such tumours but also to therapy resistance...
  71. Graus Porta D, Beerli R, Daly J, Hynes N. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J. 1997;16:1647-55 pubmed
    ..These results provide the first biochemical evidence that a given ErbB receptor has distinct signaling properties depending on its dimerization. ..
  72. Schulze W, Deng L, Mann M. Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol Syst Biol. 2005;1:2005.0008 pubmed
    ..EGFR and ErbB4 had several docking sites for Grb2, while ErbB3 was characterized by six binding sites for PI3K...
  73. Wang S, Narasanna A, Perez Torres M, Xiang B, Wu F, Yang S, et al. HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors. Cancer Cell. 2006;10:25-38 pubmed
    ..These data suggest that (1) HER2(YVMA) activates cellular substrates more potently than HER2(WT); and (2) cancer cells expressing this mutation remain sensitive to HER2-targeted therapies but insensitive to EGFR TKIs. ..
  74. Fiddes R, Campbell D, Janes P, Sivertsen S, Sasaki H, Wallasch C, et al. Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3. J Biol Chem. 1998;273:7717-24 pubmed
    ..activation of particular erbB receptor combinations was used as a model system to investigate the interaction of erbB3 and erbB4 with the adaptor protein growth factor receptor-bound (Grb)7...
  75. Cao Z, Wu X, Yen L, Sweeney C, Carraway K. Neuregulin-induced ErbB3 downregulation is mediated by a protein stability cascade involving the E3 ubiquitin ligase Nrdp1. Mol Cell Biol. 2007;27:2180-8 pubmed
    ..studies have demonstrated that the E3 ubiquitin ligase Nrdp1 contributes to the maintenance of steady-state ErbB3 levels by mediating its growth factor-independent degradation...
  76. Shi F, Telesco S, Liu Y, Radhakrishnan R, Lemmon M. ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation. Proc Natl Acad Sci U S A. 2010;107:7692-7 pubmed publisher
    b>ErbB3/HER3 is one of four members of the human epidermal growth factor receptor (EGFR/HER) or ErbB receptor tyrosine kinase family...
  77. Qiu X, Goldberg A. Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3. Proc Natl Acad Sci U S A. 2002;99:14843-8 pubmed
    ..Here, we present evidence that ErbB3 is degraded by proteasomes, and that Nrdp1 (referred to as FLRF in mice) associates with ErbB3 and stimulates its ..
  78. Smirnova T, Zhou Z, Flinn R, Wyckoff J, Boimel P, Pozzuto M, et al. Phosphoinositide 3-kinase signaling is critical for ErbB3-driven breast cancer cell motility and metastasis. Oncogene. 2012;31:706-15 pubmed publisher
    Many malignancies show increased expression of the epidermal growth factor (EGF) receptor family member ErbB3 (HER3)...
  79. Zhang Q, Park E, Kani K, Landgraf R. Functional isolation of activated and unilaterally phosphorylated heterodimers of ERBB2 and ERBB3 as scaffolds in ligand-dependent signaling. Proc Natl Acad Sci U S A. 2012;109:13237-42 pubmed publisher
    ..Heterodimers of the ligand-binding-deficient ERBB2 (HER2) receptor and the kinase impaired ERBB3 (HER3) create a potent mitogenic signal, but the phosphorylation of ERBB2 in this context presents a challenge to ..
  80. Koumakpayi I, Diallo J, Le Page C, Lessard L, Gleave M, Begin L, et al. Expression and nuclear localization of ErbB3 in prostate cancer. Clin Cancer Res. 2006;12:2730-7 pubmed
    ..The aim of this study was to analyze the expression and localization of ErbB3 in prostate tissues and prostate cancer cell lines...
  81. Addo Yobo S, Straessle J, Anwar A, Donson A, Kleinschmidt DeMasters B, Foreman N. Paired overexpression of ErbB3 and Sox10 in pilocytic astrocytoma. J Neuropathol Exp Neurol. 2006;65:769-75 pubmed
    ..Using gene expression microarray and Western blot analyses, we found that ErbB3 is highly overexpressed in PA compared with other pediatric brain tumors (glioblastoma, ependymoma, ..
  82. Sassen A, Rochon J, Wild P, Hartmann A, Hofstaedter F, Schwarz S, et al. Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients. Breast Cancer Res. 2008;10:R2 pubmed publisher of receptor tyrosine kinases (HER1/EGFR (epidermal growth factor receptor)/c-erbB1, HER2/c-erbB2, HER3/c-erbB3 and HER4/c-erbB4) shares a high degree of structural and functional homology...
  83. Wehrman T, Raab W, Casipit C, Doyonnas R, Pomerantz J, Blau H. A system for quantifying dynamic protein interactions defines a role for Herceptin in modulating ErbB2 interactions. Proc Natl Acad Sci U S A. 2006;103:19063-8 pubmed
    ..of this system to the interactions of the EGFR family showed that ErbB2 interacts stably with the EGFR and ErbB3, but fails to spontaneously homooligomerize...