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Gene Review

Nrg1  -  neuregulin 1

Mus musculus

Synonyms: 6030402G23Rik, ARIA, D230005F13Rik, GGF, GGFII, ...
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Disease relevance of Nrg1

  • The amelioration of dystrophic phenotype by heregulin-mediated utrophin up-regulation offers a pharmacological therapeutic modality and obviates many of the toxicity and delivery issues associated with viral vector-based gene therapy for DMD [1].
  • We thereby sought to determine whether overexpression of the extracellular region of HRG would be sufficient to induce mammary gland carcinomas [2].
  • A HRG construct lacking the cytoplasmic domain was targeted to the mammary gland using the murine mammary tumor virus promoter [2].
  • Based on these results, we propose that heregulin increases the expression of pro-invasive, pro-metastatic and anti-apoptotic genes in cancer cells through autocrine activation of NF-kappaB, which leads to invasive and drug-resistant growth of breast cancer [3].
  • Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas [4].

High impact information on Nrg1


Chemical compound and disease context of Nrg1


Biological context of Nrg1


Anatomical context of Nrg1


Associations of Nrg1 with chemical compounds


Physical interactions of Nrg1

  • Furthermore, the neural tube activity is blocked by a hybrid protein containing the NDF-binding domain of the ErbB4 receptor, strongly implicating NDF in the physiological transition [21].
  • Heregulin receptors are unable to mediate the rapid internalization of bound ligand as demonstrated in cells transfected with chimeric or wild-type ErbB-2, -3, or -4 receptors (Baulida et al., 1996, J. Biol. Chem. 271, 5251-5257; Pinkas-Kramanski et al., 1996, EMBO J. 15, 2452-2467) [22].

Enzymatic interactions of Nrg1

  • More Retinoblastoma protein was found in the hypophosphorylated state in the cells treated with mAb ID5, whereas more retinoblastoma protein was in the hyperphosphorylated state in heregulin-treated cells [23].
  • Furthermore, neuregulin phosphorylated CREB, a well-known down-stream transcription factor of PKA [24].

Regulatory relationships of Nrg1


Other interactions of Nrg1


Analytical, diagnostic and therapeutic context of Nrg1


  1. Heregulin ameliorates the dystrophic phenotype in mdx mice. Krag, T.O., Bogdanovich, S., Jensen, C.J., Fischer, M.D., Hansen-Schwartz, J., Javazon, E.H., Flake, A.W., Edvinsson, L., Khurana, T.S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. The extracellular region of heregulin is sufficient to promote mammary gland proliferation and tumorigenesis but not apoptosis. Weinstein, E.J., Leder, P. Cancer Res. (2000) [Pubmed]
  3. Identification of signal transduction pathways involved in constitutive NF-kappaB activation in breast cancer cells. Bhat-Nakshatri, P., Sweeney, C.J., Nakshatri, H. Oncogene (2002) [Pubmed]
  4. Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas. Balañá, M.E., Lupu, R., Labriola, L., Charreau, E.H., Elizalde, P.V. Oncogene (1999) [Pubmed]
  5. Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors. Camenisch, T.D., Schroeder, J.A., Bradley, J., Klewer, S.E., McDonald, J.A. Nat. Med. (2002) [Pubmed]
  6. The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Pattyn, A., Morin, X., Cremer, H., Goridis, C., Brunet, J.F. Nature (1999) [Pubmed]
  7. Neuregulins are concentrated at nerve-muscle synapses and activate ACh-receptor gene expression. Jo, S.A., Zhu, X., Marchionni, M.A., Burden, S.J. Nature (1995) [Pubmed]
  8. Recombinant heregulin-Pseudomonas exotoxin fusion proteins: interactions with the heregulin receptors and antitumor activity in vivo. Yang, D., Kuan, C.T., Payne, J., Kihara, A., Murray, A., Wang, L.M., Alimandi, M., Pierce, J.H., Pastan, I., Lippman, M.E. Clin. Cancer Res. (1998) [Pubmed]
  9. HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Pietras, R.J., Arboleda, J., Reese, D.M., Wongvipat, N., Pegram, M.D., Ramos, L., Gorman, C.M., Parker, M.G., Sliwkowski, M.X., Slamon, D.J. Oncogene (1995) [Pubmed]
  10. Evidence of Rab3A expression, regulation of vesicle trafficking, and cellular secretion in response to heregulin in mammary epithelial cells. Vadlamudi, R.K., Wang, R.A., Talukder, A.H., Adam, L., Johnson, R., Kumar, R. Mol. Cell. Biol. (2000) [Pubmed]
  11. Regulation of the ErbB3 binding protein Ebp1 by protein kinase C. Lessor, T.J., Hamburger, A.W. Mol. Cell. Endocrinol. (2001) [Pubmed]
  12. Heregulin is sufficient for the promotion of tumorigenicity and metastasis of breast cancer cells in vivo. Atlas, E., Cardillo, M., Mehmi, I., Zahedkargaran, H., Tang, C., Lupu, R. Mol. Cancer Res. (2003) [Pubmed]
  13. Axonal neuregulin-1 regulates myelin sheath thickness. Michailov, G.V., Sereda, M.W., Brinkmann, B.G., Fischer, T.M., Haug, B., Birchmeier, C., Role, L., Lai, C., Schwab, M.H., Nave, K.A. Science (2004) [Pubmed]
  14. The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for development of the sympathetic nervous system. Britsch, S., Li, L., Kirchhoff, S., Theuring, F., Brinkmann, V., Birchmeier, C., Riethmacher, D. Genes Dev. (1998) [Pubmed]
  15. PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2. Lynch, D.K., Daly, R.J. EMBO J. (2002) [Pubmed]
  16. Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland. Yang, Y., Spitzer, E., Meyer, D., Sachs, M., Niemann, C., Hartmann, G., Weidner, K.M., Birchmeier, C., Birchmeier, W. J. Cell Biol. (1995) [Pubmed]
  17. Heregulin induces transcriptional activation of the progesterone receptor by a mechanism that requires functional ErbB-2 and mitogen-activated protein kinase activation in breast cancer cells. Labriola, L., Salatino, M., Proietti, C.J., Pecci, A., Coso, O.A., Kornblihtt, A.R., Charreau, E.H., Elizalde, P.V. Mol. Cell. Biol. (2003) [Pubmed]
  18. A role for neuregulin1 signaling in muscle spindle differentiation. Hippenmeyer, S., Shneider, N.A., Birchmeier, C., Burden, S.J., Jessell, T.M., Arber, S. Neuron (2002) [Pubmed]
  19. Novel role for cyclin-dependent kinase 2 in neuregulin-induced acetylcholine receptor epsilon subunit expression in differentiated myotubes. Lu, G., Seta, K.A., Millhorn, D.E. J. Biol. Chem. (2005) [Pubmed]
  20. Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro. Calaora, V., Rogister, B., Bismuth, K., Murray, K., Brandt, H., Leprince, P., Marchionni, M., Dubois-Dalcq, M. J. Neurosci. (2001) [Pubmed]
  21. The regulation of Krox-20 expression reveals important steps in the control of peripheral glial cell development. Murphy, P., Topilko, P., Schneider-Maunoury, S., Seitanidou, T., Baron-Van Evercooren, A., Charnay, P. Development (1996) [Pubmed]
  22. Heregulin degradation in the absence of rapid receptor-mediated internalization. Baulida, J., Carpenter, G. Exp. Cell Res. (1997) [Pubmed]
  23. Anti-HER2 antibody and heregulin suppress growth of HER2-overexpressing human breast cancer cells through different mechanisms. Le, X.F., McWatters, A., Wiener, J., Wu, J.Y., Mills, G.B., Bast, R.C. Clin. Cancer Res. (2000) [Pubmed]
  24. Cyclic AMP-dependent protein kinase A and CREB are involved in neuregulin-induced synapse-specific expression of acetylcholine receptor gene. Kang, B.H., Jo, I., Eun, S.Y., Jo, S.A. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  25. Expression of heregulin by mouse mammary tumor cells: role in activation of ErbB receptors. Schmitt, M., Walker, M.P., Richards, R.G., Bocchinfuso, W.P., Fukuda, T., Medina, D., Kittrell, F.S., Korach, K.S., DiAugustine, R.P. Mol. Carcinog. (2006) [Pubmed]
  26. Activation of utrophin promoter by heregulin via the ets-related transcription factor complex GA-binding protein alpha/beta. Khurana, T.S., Rosmarin, A.G., Shang, J., Krag, T.O., Das, S., Gammeltoft, S. Mol. Biol. Cell (1999) [Pubmed]
  27. Neural expression and chromosomal mapping of Neu differentiation factor to 8p12-p21. Orr-Urtreger, A., Trakhtenbrot, L., Ben-Levy, R., Wen, D., Rechavi, G., Lonai, P., Yarden, Y. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  28. Induction of utrophin gene expression by heregulin in skeletal muscle cells: role of the N-box motif and GA binding protein. Gramolini, A.O., Angus, L.M., Schaeffer, L., Burton, E.A., Tinsley, J.M., Davies, K.E., Changeux, J.P., Jasmin, B.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
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