Gene Symbol: ERBB4
Description: erb-b2 receptor tyrosine kinase 4
Alias: ALS19, HER4, p180erbB4, receptor tyrosine-protein kinase erbB-4, ERBB4 transcript variant I12DEL, ERBB4 transcript variant I20DEL, avian erythroblastic leukemia viral (v-erb-b2) oncogene homolog 4, human epidermal growth factor receptor 4, proto-oncogene-like protein c-ErbB-4, tyrosine kinase-type cell surface receptor HER4, v-erb-a erythroblastic leukemia viral oncogene homolog 4, v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4
Species: human
Products:     ERBB4

Top Publications

  1. Elenius K, Corfas G, Paul S, Choi C, Rio C, Plowman G, et al. A novel juxtamembrane domain isoform of HER4/ErbB4. Isoform-specific tissue distribution and differential processing in response to phorbol ester. J Biol Chem. 1997;272:26761-8 pubmed
    b>Human epidermal growth factor receptor 4 (HER4) is a member of the epidermal growth factor (EGF) receptor subfamily of receptor tyrosine kinases that is activated by neuregulins (NRG), betacellulin (BTC), and heparin-binding EGF-like ..
  2. Junttila T, Sundvall M, Lundin M, Lundin J, Tanner M, Härkönen P, et al. Cleavable ErbB4 isoform in estrogen receptor-regulated growth of breast cancer cells. Cancer Res. 2005;65:1384-93 pubmed
    ..and ErbB2 receptors are well-characterized targets for anticancer drugs, but the clinical relevance of the related ErbB4 receptor is unknown...
  3. Ferretti E, Di Marcotullio L, Gessi M, Mattei T, Greco A, Po A, et al. Alternative splicing of the ErbB-4 cytoplasmic domain and its regulation by hedgehog signaling identify distinct medulloblastoma subsets. Oncogene. 2006;25:7267-73 pubmed
    ..These findings demonstrate that low-level Hh signalling in human MB is associated with the selective maintenance of high ErbB-4 CYT-1 expression, an alteration that exerts tumor-promoting effects. ..
  4. Sundvall M, Korhonen A, Paatero I, Gaudio E, Melino G, Croce C, et al. Isoform-specific monoubiquitination, endocytosis, and degradation of alternatively spliced ErbB4 isoforms. Proc Natl Acad Sci U S A. 2008;105:4162-7 pubmed publisher
    ..Here we demonstrate that endocytosis of ErbB4 is regulated in an isoform-specific manner: CYT-1 isoforms were efficiently endocytosed whereas CYT-2 isoforms ..
  5. Zhu Y, Sullivan L, Nair S, Williams C, Pandey A, Marrero L, et al. Coregulation of estrogen receptor by ERBB4/HER4 establishes a growth-promoting autocrine signal in breast tumor cells. Cancer Res. 2006;66:7991-8 pubmed
    ..between extranuclear estrogen receptor alpha (ER) and the epidermal growth factor receptor (EGFR) family member ERBB4. Ectopically expressed as well as endogenous ERBB4 interacts with and potentiates ER transactivation, indicating ..
  6. Rokavec M, Justenhoven C, Schroth W, Istrate M, Haas S, Fischer H, et al. A novel polymorphism in the promoter region of ERBB4 is associated with breast and colorectal cancer risk. Clin Cancer Res. 2007;13:7506-14 pubmed
    The receptor tyrosine kinase ERBB4/HER4 plays a role in cell division, migration, differentiation, as well as apoptosis, and is frequently overexpressed in breast and colorectal tumors...
  7. Muraoka Cook R, Sandahl M, Strunk K, Miraglia L, Husted C, Hunter D, et al. ErbB4 splice variants Cyt1 and Cyt2 differ by 16 amino acids and exert opposing effects on the mammary epithelium in vivo. Mol Cell Biol. 2009;29:4935-48 pubmed publisher
    Data concerning the prognostic value of ErbB4 in breast cancer and effects on cell growth have varied in published reports, perhaps due to the unknown signaling consequences of expression of the intracellular proteolytic ErbB4 s80(HER4) ..
  8. Frey M, Edelblum K, Mullane M, Liang D, Polk D. The ErbB4 growth factor receptor is required for colon epithelial cell survival in the presence of TNF. Gastroenterology. 2009;136:217-26 pubmed publisher
    The ErbB4 receptor tyrosine kinase regulates cell growth, survival, and differentiation in several tissues, but its role in the gastrointestinal tract has not been reported...
  9. Hollmen M, Liu P, Kurppa K, Wildiers H, Reinvall I, Vandorpe T, et al. Proteolytic processing of ErbB4 in breast cancer. PLoS ONE. 2012;7:e39413 pubmed publisher
    b>ErbB4 is a receptor tyrosine kinase that can signal by a mechanism involving proteolytic release of intracellular and extracellular receptor fragments...

More Information


  1. Kainulainen V, Sundvall M, Määttä J, Santiestevan E, Klagsbrun M, Elenius K. A natural ErbB4 isoform that does not activate phosphoinositide 3-kinase mediates proliferation but not survival or chemotaxis. J Biol Chem. 2000;275:8641-9 pubmed
    b>ErbB4 is a member of the epidermal growth factor receptor (ErbB) family that mediates cellular responses activated by neuregulins (NRG) and other epidermal growth factor-like growth factors...
  2. Murabito J, Rosenberg C, Finger D, Kreger B, Levy D, Splansky G, et al. A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study. BMC Med Genet. 2007;8 Suppl 1:S6 pubmed
    ..008 and rs2410373, FBAT p = 0.021) were associated with prostate cancer and three ERBB4 SNPs (rs905883 GEE p = 0.0002, rs7564590 GEE p = 0.003, rs7558615 GEE p = 0...
  3. Vidal G, Naresh A, Marrero L, Jones F. Presenilin-dependent gamma-secretase processing regulates multiple ERBB4/HER4 activities. J Biol Chem. 2005;280:19777-83 pubmed
    ..The receptor tyrosine kinase ERBB4/HER4 (referred to here as ERBB4) undergoes sequential processing by tumor necrosis factor-alpha converting enzyme ..
  4. Laederich M, Funes Duran M, Yen L, Ingalla E, Wu X, Carraway K, et al. The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases. J Biol Chem. 2004;279:47050-6 pubmed
    ..also called Lig-1) protein can act as a negative regulator of EGF receptor and its relatives, ErbB2, ErbB3, and ErbB4. We observed that in co-transfected 293T cells, LRIG1 forms a complex with each of the ErbB receptors independent ..
  5. Hahn C, Wang H, Cho D, Talbot K, Gur R, Berrettini W, et al. Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat Med. 2006;12:824-8 pubmed
    ..Among NRG1 receptors, erbB4 is of particular interest because of its crucial roles in neurodevelopment and in the modulation of N-methyl-D-..
  6. Omerovic J, Santangelo L, Puggioni E, Marrocco J, Dall Armi C, Palumbo C, et al. The E3 ligase Aip4/Itch ubiquitinates and targets ErbB-4 for degradation. FASEB J. 2007;21:2849-62 pubmed
    ..These findings expand our understanding of the mechanisms contributing to the integrity of the ErbB signaling network and mechanistically link the cellular ubiquitination pathway of AIP4/Itch to the ErbB-4 receptor. ..
  7. Gallo R, Bryant I, Fry R, Williams E, Riese D. Phosphorylation of ErbB4 on Tyr1056 is critical for inhibition of colony formation by prostate tumor cell lines. Biochem Biophys Res Commun. 2006;349:372-82 pubmed
    We have previously demonstrated that the constitutively active Q646C mutant of the ErbB4 receptor tyrosine kinase inhibits colony formation by human prostate tumor cell lines...
  8. Nicodemus K, Law A, Radulescu E, Luna A, Kolachana B, Vakkalanka R, et al. Biological validation of increased schizophrenia risk with NRG1, ERBB4, and AKT1 epistasis via functional neuroimaging in healthy controls. Arch Gen Psychiatry. 2010;67:991-1001 pubmed publisher
    ..between NRG1 and selected N-methyl-d-aspartate-glutamate pathway partners implicated in its effects, including ERBB4, AKT1, DLG4, NOS1, and NOS1AP...
  9. Harari D, Tzahar E, Romano J, Shelly M, Pierce J, Andrews G, et al. Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase. Oncogene. 1999;18:2681-9 pubmed
    ..The primary structure and the pattern of expression of NRG-4, together with the strict specificity of this growth factor to ErbB-4, suggest a physiological role distinct from that of the known ErbB ligands. ..
  10. Clark D, Williams C, Duplessis T, Moring K, Notwick A, Long W, et al. ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events. J Biol Chem. 2005;280:24175-80 pubmed
    The epidermal growth factor receptor family member ERBB4 is required for mammary gland development and lactation...
  11. Kaushansky A, Gordus A, Budnik B, Lane W, Rush J, MacBeath G. System-wide investigation of ErbB4 reveals 19 sites of Tyr phosphorylation that are unusually selective in their recruitment properties. Chem Biol. 2008;15:808-17 pubmed publisher
    ..Much less is known about ErbB4. Here we use tandem mass spectrometry to identify 19 sites of tyrosine phosphorylation on ErbB4, and protein ..
  12. Williams C, Allison J, Vidal G, Burow M, Beckman B, Marrero L, et al. The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone. J Cell Biol. 2004;167:469-78 pubmed
    In the lactating breast, ERBB4 localizes to the nuclei of secretory epithelium while regulating activities of the signal transducer and activator of transcription (STAT) 5A transcription factor essential for milk-gene expression...
  13. Feng S, Muraoka Cook R, Hunter D, Sandahl M, Caskey L, Miyazawa K, et al. The E3 ubiquitin ligase WWP1 selectively targets HER4 and its proteolytically derived signaling isoforms for degradation. Mol Cell Biol. 2009;29:892-906 pubmed publisher
    In general, epidermal growth factor receptor family members stimulate cell proliferation. In contrast, at least one HER4 isoform, JM-a/Cyt1, inhibits cell growth after undergoing a two-step proteolytic cleavage that first produces a ..
  14. Srinivasan R, Benton E, McCormick F, Thomas H, Gullick W. Expression of the c-erbB-3/HER-3 and c-erbB-4/HER-4 growth factor receptors and their ligands, neuregulin-1 alpha, neuregulin-1 beta, and betacellulin, in normal endometrium and endometrial cancer. Clin Cancer Res. 1999;5:2877-83 pubmed
    ..These results suggest that signaling through the c-erbB-3 and c-erbB-4 receptors and the ligands neuregulin alpha, neuregulin beta, and betacellulin are important in endometrial carcinogenesis. ..
  15. 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. ..
  16. 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
    ..Furthermore, a monoclonal ErbB3-directed antibody (MM-121) also significantly inhibited tumor growth in vivo. These findings identify ErbB3 as a potential therapeutic target in ovarian cancer. ..
  17. Feng S, Sartor C, Hunter D, Zhou H, Yang X, Caskey L, et al. The HER4 cytoplasmic domain, but not its C terminus, inhibits mammary cell proliferation. Mol Endocrinol. 2007;21:1861-76 pubmed
    Unlike the proliferative action of other epidermal growth factor (EGF) receptor family members, HER4/ErbB4 is often associated with growth-inhibitory and differentiation signaling...
  18. Prickett T, Agrawal N, Wei X, Yates K, Lin J, Wunderlich J, et al. Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nat Genet. 2009;41:1127-32 pubmed publisher
    ..We found ERBB4 mutations in 19% of individuals with melanoma and found mutations in two other kinases (FLT1 and PTK2B) in 10% of ..
  19. Sundvall M, Veikkolainen V, Kurppa K, Salah Z, Tvorogov D, van Zoelen E, et al. Cell death or survival promoted by alternative isoforms of ErbB4. Mol Biol Cell. 2010;21:4275-86 pubmed publisher
    The significance of ErbB4 in tumor biology is poorly understood. The ERBB4 gene is alternatively spliced producing juxtamembrane (JM-a and JM-b) and cytoplasmic (CYT-1 and CYT-2) isoforms...
  20. Muraoka Cook R, Caskey L, Sandahl M, Hunter D, Husted C, Strunk K, et al. Heregulin-dependent delay in mitotic progression requires HER4 and BRCA1. Mol Cell Biol. 2006;26:6412-24 pubmed
    b>HER4 expression in human breast cancers correlates with a positive prognosis. While heregulin inhibits the growth of HER4-positive breast cancer cells, it does so by undefined mechanisms...
  21. Vidal G, Clark D, Marrero L, Jones F. A constitutively active ERBB4/HER4 allele with enhanced transcriptional coactivation and cell-killing activities. Oncogene. 2007;26:462-6 pubmed
    In the normal breast, ERBB4 regulates epithelial differentiation and functions as a nuclear chaperone for signal transducer and activator of transcription (STAT) 5A, thereby stimulating milk-gene expression...
  22. Srinivasan R, Poulsom R, Hurst H, Gullick W. Expression of the c-erbB-4/HER4 protein and mRNA in normal human fetal and adult tissues and in a survey of nine solid tumour types. J Pathol. 1998;185:236-45 pubmed
    The c-erbB-4/HER4 receptor belongs to the family of the type I growth factor receptors...
  23. Lu C, Wang Y, Chen J, Lai I, Liou Y. Support for the involvement of the ERBB4 gene in schizophrenia: a genetic association analysis. Neurosci Lett. 2010;481:120-5 pubmed publisher
    ..The aim of the present study was to examine whether genetic variation in the human ERBB4 gene is associated with susceptibility to schizophrenia...
  24. Silberberg G, Darvasi A, Pinkas Kramarski R, Navon R. The involvement of ErbB4 with schizophrenia: association and expression studies. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:142-8 pubmed
    ..Consistently, mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia...
  25. Tvorogov D, Sundvall M, Kurppa K, Hollmen M, Repo S, Johnson M, et al. Somatic mutations of ErbB4: selective loss-of-function phenotype affecting signal transduction pathways in cancer. J Biol Chem. 2009;284:5582-91 pubmed publisher
    ..However, the role of ErbB4 as a potential cancer drug target has remained controversial...
  26. 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. ..
  27. Law A, Kleinman J, Weinberger D, Weickert C. Disease-associated intronic variants in the ErbB4 gene are related to altered ErbB4 splice-variant expression in the brain in schizophrenia. Hum Mol Genet. 2007;16:129-41 pubmed
    The neuregulin 1 (NRG1) receptor, ErbB4, has been identified as a potential risk gene for schizophrenia. HER4/ErbB4 is a receptor tyrosine kinase whose transcript undergoes alternative splicing in the brain...
  28. Konrad A, Vucurevic G, Musso F, Stoeter P, Dahmen N, Winterer G. ErbB4 genotype predicts left frontotemporal structural connectivity in human brain. Neuropsychopharmacology. 2009;34:641-50 pubmed publisher
    ..Several investigations have suggested that variations of the genes that encode the Neuregulin 1 (NRG1)-ErbB4 receptor complex are associated with schizophrenia illness...
  29. Tovey S, Dunne B, Witton C, Cooke T, Bartlett J. HER4 in breast cancer: comparison of antibodies against intra- and extra-cellular domains of HER4. Breast Cancer Res. 2006;8:R19 pubmed
    We have previously linked HER4 expression with increased survival in breast cancer. However, other reports have associated HER4 with adverse prognostic significance...
  30. Maatta J, Olli K, Henttinen T, Tuittila M, Elenius K, Salmivirta M. Removal of cell surface heparan sulfate increases TACE activity and cleavage of ErbB4 receptor. BMC Cell Biol. 2009;10:5 pubmed publisher
    Nuclear localization of proteolytically formed intracellular fragment of ErbB4 receptor tyrosine kinase has been shown to promote cell survival, and nuclear localization of ErbB4 receptor has been described in human breast cancer...
  31. Bouyain S, Longo P, Li S, Ferguson K, Leahy D. The extracellular region of ErbB4 adopts a tethered conformation in the absence of ligand. Proc Natl Acad Sci U S A. 2005;102:15024-9 pubmed
    ..kinases comprises the epidermal growth factor receptor (EGFR/ErbB1/HER1), ErbB2 (HER2/Neu), ErbB3 (HER3), and ErbB4 (HER4)...
  32. 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
    ..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 cell lines, suggesting the ..
  33. Linggi B, Cheng Q, Rao A, Carpenter G. The ErbB-4 s80 intracellular domain is a constitutively active tyrosine kinase. Oncogene. 2006;25:160-3 pubmed
    ..This is the first example of constitutive kinase activation and dimerization totally within the cytoplasmic domain of an ErbB receptor and suggests that the s80 ICD may function to phosphorylate substrates in the cytoplasm or nucleus. ..
  34. Tovey S, Witton C, Bartlett J, Stanton P, Reeves J, Cooke T. Outcome and human epidermal growth factor receptor (HER) 1-4 status in invasive breast carcinomas with proliferation indices evaluated by bromodeoxyuridine labelling. Breast Cancer Res. 2004;6:R246-51 pubmed
    ..of human epidermal growth factor receptor (HER)1, HER2 and HER3 is associated with poor prognosis in breast cancer, HER4 is associated with a good prognosis...
  35. Cheng Q, Tikhomirov O, Zhou W, Carpenter G. Ectodomain cleavage of ErbB-4: characterization of the cleavage site and m80 fragment. J Biol Chem. 2003;278:38421-7 pubmed
    ..When the m80 ErbB-4 fragment is generated by cell treatment with heregulin or 12-O-tetradecanoylphorbol-13-acetate, the fragment associates with intact ErbB-2. However, this fragment does not associate with the intact ErbB-4 molecule. ..
  36. Rokicki J, Das P, Giltnane J, Wansbury O, Rimm D, Howard B, et al. The ERalpha coactivator, HER4/4ICD, regulates progesterone receptor expression in normal and malignant breast epithelium. Mol Cancer. 2010;9:150 pubmed publisher
    The HER4 intracellular domain (4ICD) is a potent estrogen receptor (ERalpha) coactivator with activities in breast cancer and the developing mammary gland that appear to overlap with progesterone receptor (PgR)...
  37. Carpenter G. ErbB-4: mechanism of action and biology. Exp Cell Res. 2003;284:66-77 pubmed
  38. Ni C, Yuan H, Carpenter G. Role of the ErbB-4 carboxyl terminus in gamma-secretase cleavage. J Biol Chem. 2003;278:4561-5 pubmed
  39. Zhang D, Sliwkowski M, Mark M, Frantz G, Akita R, Sun Y, et al. Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4. Proc Natl Acad Sci U S A. 1997;94:9562-7 pubmed
    ..The biological effects of NRG1 are mediated by receptor tyrosine kinases ErbB2, ErbB3, and ErbB4. However, genetic studies have suggested that the activity of ErbB4 may also be regulated in the central nervous ..
  40. Sassen A, Diermeier Daucher S, Sieben M, Ortmann O, Hofstaedter F, Schwarz S, et al. Presence of HER4 associates with increased sensitivity to Herceptin in patients with metastatic breast cancer. Breast Cancer Res. 2009;11:R50 pubmed publisher
    ..investigated in this study Kaplan-Meier and Cox regression analysis revealed a significant positive impact of HER4 (co-)expression on overall survival from beginning of antibody therapy...
  41. Das P, Thor A, Edgerton S, Barry S, Chen D, Jones F. Reactivation of epigenetically silenced HER4/ERBB4 results in apoptosis of breast tumor cells. Oncogene. 2010;29:5214-9 pubmed publisher
    Experimental and clinical data support a growth inhibitory role for HER4 in breast cancer...
  42. 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
    ..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...
  43. Machleidt A, Buchholz S, Diermeier Daucher S, Zeman F, Ortmann O, Brockhoff G. The prognostic value of Her4 receptor isoform expression in triple-negative and Her2 positive breast cancer patients. BMC Cancer. 2013;13:437 pubmed publisher
    ..described to be expressed in a variety of normal and neoplastic tissues: Her1, Her2, Her3, and additionally four Her4 isoforms have been identified...
  44. Muraoka Cook R, Sandahl M, Husted C, Hunter D, Miraglia L, Feng S, et al. The intracellular domain of ErbB4 induces differentiation of mammary epithelial cells. Mol Biol Cell. 2006;17:4118-29 pubmed
    Differentiation of mammary epithelium in vivo requires signaling through prolactin- and ErbB4/HER4-dependent mechanisms; how these pathways intersect is unknown...
  45. Barnes N, Khavari S, Boland G, Cramer A, Knox W, Bundred N. Absence of HER4 expression predicts recurrence of ductal carcinoma in situ of the breast. Clin Cancer Res. 2005;11:2163-8 pubmed
    ..c-erbB2/neu) is associated with resistance to hormone therapy and poor survival in invasive breast cancer, whereas HER4 expression is associated with endocrine responsiveness...
  46. Norton N, Moskvina V, Morris D, Bray N, Zammit S, Williams N, et al. Evidence that interaction between neuregulin 1 and its receptor erbB4 increases susceptibility to schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:96-101 pubmed
    ..NRG1 mediates some of its effects through the tyrosine kinase receptor erbB4, and analysis of gene knock-out animals suggests that the functional interaction of NRG1 and erbB4 mediates ..
  47. Maatta J, Sundvall M, Junttila T, Peri L, Laine V, Isola J, et al. Proteolytic cleavage and phosphorylation of a tumor-associated ErbB4 isoform promote ligand-independent survival and cancer cell growth. Mol Biol Cell. 2006;17:67-79 pubmed
    ..are oncogenes with therapeutic significance in human cancer, whereas the transforming potential of the related ErbB4 receptor has remained controversial...
  48. Benzel I, Bansal A, Browning B, Galwey N, Maycox P, McGinnis R, et al. Interactions among genes in the ErbB-Neuregulin signalling network are associated with increased susceptibility to schizophrenia. Behav Brain Funct. 2007;3:31 pubmed
    ..several recent reports suggest association between schizophrenia and single-nucleotide polymorphisms (SNPs) in ERBB4, one of the receptors for Neuregulin-1...
  49. 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
    ..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...
  50. Hua Y, Gorshkov K, Yang Y, Wang W, Zhang N, Hughes D. Slow down to stay alive: HER4 protects against cellular stress and confers chemoresistance in neuroblastoma. Cancer. 2012;118:5140-54 pubmed publisher
    ..basis of previous work and on data from publicly available studies, the authors hypothesized that human epidermal growth factor receptor 4 (Her4) contributes to resistance...
  51. Elenius K, Choi C, Paul S, Santiestevan E, Nishi E, Klagsbrun M. Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase. Oncogene. 1999;18:2607-15 pubmed
    ..Epidermal growth factor (EGF) receptor tyrosine kinases include ErbB1, ErbB2, ErbB3 and ErbB4. ErbB4 is a tyrosine kinase receptor that binds neuregulins (NRG) and several other EGF family members...
  52. Arasada R, Carpenter G. Secretase-dependent tyrosine phosphorylation of Mdm2 by the ErbB-4 intracellular domain fragment. J Biol Chem. 2005;280:30783-7 pubmed
    ..In addition, expression of the ICD fragment increased p53 activity toward the p21 promoter in a luciferase reporter assay. ..
  53. Aqeilan R, Donati V, Palamarchuk A, Trapasso F, Kaou M, Pekarsky Y, et al. WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res. 2005;65:6764-72 pubmed
    ..In summary, our data indicate that WWOX antagonizes the function of YAP by competing for interaction with ErbB-4 and other targets and thus affect its transcriptional activity. ..
  54. Starr A, Greif J, Vexler A, Ashkenazy Voghera M, Gladesh V, Rubin C, et al. ErbB4 increases the proliferation potential of human lung cancer cells and its blockage can be used as a target for anti-cancer therapy. Int J Cancer. 2006;119:269-74 pubmed
    ..The results of the current study provide evidence that ErbB-4 plays a significant role in human lung cancer and may serve as a molecular target for anticancer therapy. ..
  55. Yumoto N, Yu X, Hatakeyama M. Expression of the ErbB4 receptor causes reversal regulation of PP2A in the Shc signal transduction pathway in human cancer cells. Mol Cell Biochem. 2006;285:165-71 pubmed
    Expression of ErbB4 receptor is correlated with the incidence of non-metastatic types of human cancers, whereas the overexpression of other ErbB receptor families (ErbB1/EGFR, ErbB2 and ErbB3) is correlated to the formation of metastatic ..
  56. 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
    ..HER3 and HER4 mRNA level had a favourable prognostic value in terms of OS and disease-free survival (DFS), respectively...
  57. 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...
  58. Zeng F, Zhang M, Singh A, Zent R, Harris R. ErbB4 isoforms selectively regulate growth factor induced Madin-Darby canine kidney cell tubulogenesis. Mol Biol Cell. 2007;18:4446-56 pubmed
    b>ErbB4, a member of the epidermal growth factor (EGF) receptor family that can be activated by heregulin beta1 and heparin binding (HB)-EGF, is expressed as alternatively spliced isoforms characterized by variant extracellular ..
  59. Sardi S, Murtie J, Koirala S, Patten B, Corfas G. Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain. Cell. 2006;127:185-97 pubmed
    ..Upon neuregulin-induced activation and presenilin-dependent cleavage of ErbB4, the receptor's intracellular domain forms a complex with TAB2 and the corepressor N-CoR...
  60. Zeng F, Xu J, Harris R. Nedd4 mediates ErbB4 JM-a/CYT-1 ICD ubiquitination and degradation in MDCK II cells. FASEB J. 2009;23:1935-45 pubmed publisher
    b>ErbB4, a type I transmembrane receptor tyrosine kinase, is a member of the epidermal growth factor receptor family...
  61. Naresh A, Long W, Vidal G, Wimley W, Marrero L, Sartor C, et al. The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein promoting apoptosis of breast cancer cells. Cancer Res. 2006;66:6412-20 pubmed
    b>ERBB4/HER4 (referred to here as ERBB4) is a unique member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. In contrast to the other three members of the EGFR family (i.e...
  62. Williams E, Trout L, Gallo R, Pitfield S, Bryant I, Penington D, et al. A constitutively active ErbB4 mutant inhibits drug-resistant colony formation by the DU-145 and PC-3 human prostate tumor cell lines. Cancer Lett. 2003;192:67-74 pubmed
    b>ErbB4 (HER4) is a member of the ErbB family of receptor tyrosine kinases, a family that also includes the Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1), Neu/ErbB2/HER2, and ErbB3/HER3...
  63. Plowman G, Culouscou J, Whitney G, Green J, Carlton G, Foy L, et al. Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci U S A. 1993;90:1746-50 pubmed
    ..The HER4/erbB4 gene encodes a 180-kDa transmembrane tyrosine kinase (HER4/p180erbB4) whose extracellular domain is most similar to the orphan receptor HER3/p160erbB3, whereas its cytoplasmic ..
  64. Paatero I, Lassus H, Junttila T, Kaskinen M, Butzow R, Elenius K. CYT-1 isoform of ErbB4 is an independent prognostic factor in serous ovarian cancer and selectively promotes ovarian cancer cell growth in vitro. Gynecol Oncol. 2013;129:179-87 pubmed publisher
    b>ErbB4 is a member of the ErbB subfamily of receptor tyrosine kinases with a poorly understood biological role in ovarian cancer...
  65. Cohen B, Green J, Foy L, Fell H. HER4-mediated biological and biochemical properties in NIH 3T3 cells. Evidence for HER1-HER4 heterodimers. J Biol Chem. 1996;271:4813-8 pubmed
    ..The most recent addition to this family of receptors, HER4, was expressed in NIH 3T3 cells to determine its biological and biochemical characteristics...
  66. Ni C, Murphy M, Golde T, Carpenter G. gamma -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science. 2001;294:2179-81 pubmed
    ..Inhibition of gamma-secretase also prevented growth inhibition by HRG. gamma-Secretase cleavage of ErbB-4 may represent another mechanism for receptor tyrosine kinase-mediated signaling. ..
  67. Lee H, Jung K, Huang Y, Bennett L, Lee J, Mei L, et al. Presenilin-dependent gamma-secretase-like intramembrane cleavage of ErbB4. J Biol Chem. 2002;277:6318-23 pubmed
    ..Here we report that ErbB4, a tyrosine kinase receptor for neuregulins, is a substrate for presenilin-dependent gamma-secretase...
  68. Frey M, Hilliard V, Mullane M, Polk D. ErbB4 promotes cyclooxygenase-2 expression and cell survival in colon epithelial cells. Lab Invest. 2010;90:1415-24 pubmed publisher
    The ErbB4 receptor tyrosine kinase is expressed at high levels in human and mouse colitis, and inhibits colon epithelial cell apoptosis in the presence of proinflammatory cytokines...
  69. Komuro A, Nagai M, Navin N, Sudol M. WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J Biol Chem. 2003;278:33334-41 pubmed
    ..The YAP.ErbB4 complex is mediated by the first WW domain of YAP and the most carboxyl-terminal PPXY motif of ErbB-4...
  70. Thor A, Edgerton S, Jones F. Subcellular localization of the HER4 intracellular domain, 4ICD, identifies distinct prognostic outcomes for breast cancer patients. Am J Pathol. 2009;175:1802-9 pubmed publisher
    Conflicting reports of the prognostic value of HER4 in breast cancer may be explained by distinct activities of the HER4 intracellular domain, 4ICD...
  71. Soung Y, Lee J, Kim S, Wang Y, Jo K, Moon S, et al. Somatic mutations of the ERBB4 kinase domain in human cancers. Int J Cancer. 2006;118:1426-9 pubmed
    The EGFR family consists of 4 receptor tyrosine kinases, EGFR (ERBB1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4)...
  72. Kim H, Lee J, Sung H, Choi J, Park S, Lee K, et al. A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study. Breast Cancer Res. 2012;14:R56 pubmed
    ..SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1...
  73. Rickman O, Vohra P, Sanyal B, Vrana J, Aubry M, Wigle D, et al. Analysis of ErbB receptors in pulmonary carcinoid tumors. Clin Cancer Res. 2009;15:3315-24 pubmed publisher
    ..atypical carcinoid (n = 7) tumor tissues were analyzed by immunohistochemical staining for EGFR, ErbB2, ErbB3, and ErbB4. Sequencing of tumor DNA of exons 18 to 21 of the EGFR gene and the KRAS gene was carried out...