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ErbB Membrane Tyrosine Kinase Receptors: Analyzing Migration in a Highly Complex Signaling System

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Protein Kinase Technologies

Part of the book series: Neuromethods ((NM,volume 68))

Abstract

The erbB membrane tyrosine kinases (EGF receptor, erbB2, erbB3, and erbB4) are a family of structurally similar transmembrane proteins that act as receptors for the EGF and neuregulin (NRG) families of growth factors. ErbB receptors and their ligands are widely expressed by neurons and glia throughout the peripheral and central nervous system, where they promote proliferation, survival, migration, differentiation, and other effects. Precisely which effects are induced by erbB activation depends on a variety of factors. These factors include which erbB receptors are recruited to the signaling complex, whether key non-erbB intramembranous proteins (e.g., mucin 1, CD44, integrins) are present and interact with the erbB kinases and the lineage and developmental state of the cell. Different erbB ligands acting through the same receptors often also elicit distinct or even diametrically opposed effects. In this chapter, we review key aspects of the complexity intrinsic to signaling by erbB kinases and their ligands in the nervous system. We then relate this knowledge to the rational design of experiments examining erbB signaling in migration, a common response induced by erbB receptor activation. The proper performance of Boyden chamber assays is considered, together with the procedures used to identify appropriate migration substrates and to optimize key experimental parameters (cell number, migration time, comparisons of the effects of different erbB ligands, and establishing optimal concentrations of these growth factors). The use of pharmacologic inhibitors and RNA interference to establish whether specific erbB kinases are required for the migration of nervous system cells is also described.

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References

  1. Gerecke KM, Wyss JM, Karavanova I, Buonanno A, Carroll SL (2001) ErbB transmembrane tyrosine kinase receptors are differentially expressed throughout the adult rat central nervous system. J Comp Neurol 433:86–100

    Article  PubMed  CAS  Google Scholar 

  2. Golding JP, Trainor P, Krumlauf R, Gassmann M (2000) Defects in pathfinding by cranial neural crest cells in mice lacking the neuregulin receptor ErbB4. Nat Cell Biol 2:103–109

    Article  PubMed  CAS  Google Scholar 

  3. Rio C, Rieff HI, Qi P, Khurana TS, Corfas G (1997) Neuregulin and erbB receptors play a critical role in neuronal migration. Neuron 19:39–50

    Article  PubMed  CAS  Google Scholar 

  4. Anton ES, Marchionni MA, Lee KF, Rakic P (1997) Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex. Development 124:3501–3510

    PubMed  CAS  Google Scholar 

  5. Gierdalski M, Sardi SP, Corfas G, Juliano SL (2005) Endogenous neuregulin restores radial glia in a (ferret) model of cortical dysplasia. J Neurosci 25:8498–8504

    Article  PubMed  CAS  Google Scholar 

  6. Schmid RS, McGrath B, Berechid BE, Boyles B, Marchionni M, Sestan N, Anton ES (2003) Neuregulin 1-erbB2 signaling is required for the establishment of radial glia and their transformation into astrocytes in cerebral cortex. Proc Natl Acad Sci U S A 100:4251–4256

    Article  PubMed  CAS  Google Scholar 

  7. Yau HJ, Wang HF, Lai C, Liu FC (2003) Neural development of the neuregulin receptor ErbB4 in the cerebral cortex and the hippocampus: preferential expression by interneurons tangentially migrating from the ganglionic eminences. Cereb Cortex 13:252–264

    Article  PubMed  Google Scholar 

  8. Flames N, Long JE, Garratt AN, Fischer TM, Gassmann M, Birchmeier C, Lai C, Rubenstein JL, Marin O (2004) Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1. Neuron 44:251–261

    Article  PubMed  CAS  Google Scholar 

  9. Anton ES, Ghashghaei HT, Weber JL, McCann C, Fischer TM, Cheung ID, Gassmann M, Messing A, Klein R, Schwab MH, Lloyd KC, Lai C (2004) Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain. Nat Neurosci 7:1319–1328

    Article  PubMed  CAS  Google Scholar 

  10. Gerecke KM, Wyss JM, Carroll SL (2004) Neuregulin-1beta induces neurite extension and arborization in cultured hippocampal neurons. Mol Cell Neurosci 27:379–393

    Article  PubMed  CAS  Google Scholar 

  11. Bermingham-McDonogh O, McCabe KL, Reh TA (1996) Effects of GGF/neuregulins on neuronal survival and neurite outgrowth correlate with erbB2/neu expression in developing rat retina. Development 122:1427–1438

    PubMed  CAS  Google Scholar 

  12. Rieff HI, Raetzman LT, Sapp DW, Yeh HH, Siegel RE, Corfas G (1999) Neuregulin induces GABA(A) receptor subunit expression and neurite outgrowth in cerebellar granule cells. J Neurosci 19:10757–10766

    PubMed  CAS  Google Scholar 

  13. Lopez-Bendito G, Cautinat A, Sanchez JA, Bielle F, Flames N, Garratt AN, Talmage DA, Role LW, Charnay P, Marin O, Garel S (2006) Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation. Cell 125:127–142

    Article  PubMed  CAS  Google Scholar 

  14. Ozaki M, Sasner M, Yano R, Lu HS, Buonanno A (1997) Neuregulin-beta induces expression of an NMDA-receptor subunit. Nature 390:691–694

    PubMed  CAS  Google Scholar 

  15. Ozaki M, Tohyama K, Kishida H, Buonanno A, Yano R, Hashikawa T (2000) Roles of neuregulin in synaptogenesis between mossy fibers and cerebellar granule cells. J Neurosci Res 59:612–623

    Article  PubMed  CAS  Google Scholar 

  16. Yang X, Kuo Y, Devay P, Yu C, Role L (1998) A cysteine-rich isoform of neuregulin controls the level of expression of neuronal nicotinic receptor channels during synaptogenesis. Neuron 20:255–270

    Article  PubMed  CAS  Google Scholar 

  17. Subramony P, Dryer SE (1997) Neuregulins stimulate the functional expression of Ca2+-activated K+ channels in developing chicken parasympathetic neurons. Proc Natl Acad Sci U S A 94:5934–5938

    Article  PubMed  CAS  Google Scholar 

  18. Cameron JS, Lhuillier L, Subramony P, Dryer SE (1998) Developmental regulation of neuronal K+ channels by target-derived TGF beta in vivo and in vitro. Neuron 21:1045–1053

    Article  PubMed  CAS  Google Scholar 

  19. Kwon OB, Paredes D, Gonzalez CM, Neddens J, Hernandez L, Vullhorst D, Buonanno A (2008) Neuregulin-1 regulates LTP at CA1 hippocampal synapses through activation of dopamine D4 receptors. Proc Natl Acad Sci U S A 105:15587–15592

    Article  PubMed  CAS  Google Scholar 

  20. Dong Z, Brennan A, Liu N, Yarden Y, Lefkowitz G, Mirsky R, Jessen KR (1995) Neu differentiation factor is a neuron-glia signal and regulates survival, proliferation, and maturation of rat Schwann cell precursors. Neuron 15:585–596

    Article  PubMed  CAS  Google Scholar 

  21. Grinspan JB, Marchionni MA, Reeves M, Coulaloglou M, Scherer SS (1996) Axonal interactions regulate Schwann cell apoptosis in developing peripheral nerve: neuregulin receptors and the role of neuregulins. J Neurosci 16:6107–6118

    PubMed  CAS  Google Scholar 

  22. Syroid DE, Maycox PR, Burrola PG, Liu N, Wen D, Lee KF, Lemke G, Kilpatrick TJ (1996) Cell death in the Schwann cell lineage and its regulation by neuregulin. Proc Natl Acad Sci U S A 93:9229–9234

    Article  PubMed  CAS  Google Scholar 

  23. Li Y, Tennekoon GI, Birnbaum M, Marchionni MA, Rutkowski JL (2001) Neuregulin signaling through a PI3K/Akt/Bad pathway in Schwann cell survival. Mol Cell Neurosci 17:761–767

    Article  PubMed  Google Scholar 

  24. Maurel P, Salzer JL (2000) Axonal regulation of Schwann cell proliferation and survival and the initial events of myelination requires PI 3-kinase activity. J Neurosci 20:4635–4645

    PubMed  CAS  Google Scholar 

  25. Meintanis S, Thomaidou D, Jessen KR, Mirsky R, Matsas R (2001) The neuron-glia signal beta-neuregulin promotes Schwann cell motility via the MAPK pathway. Glia 34:39–51

    Article  PubMed  CAS  Google Scholar 

  26. Ogata T, Iijima S, Hoshikawa S, Miura T, Yamamoto S, Oda H, Nakamura K, Tanaka S (2004) Opposing extracellular signal-regulated kinase and Akt pathways control Schwann cell myelination. J Neurosci 24:6724–6732

    Article  PubMed  CAS  Google Scholar 

  27. Vartanian T, Goodearl A, Lefebvre S, Park SK, Fischbach G (2000) Neuregulin induces the rapid association of focal adhesion kinase with the erbB2-erbB3 receptor complex in schwann cells. Biochem Biophys Res Commun 271:414–417

    Article  PubMed  CAS  Google Scholar 

  28. Michailov GV, Sereda MW, Brinkmann BG, Fischer TM, Haug B, Birchmeier C, Role L, Lai C, Schwab MH, Nave KA (2004) Axonal neuregulin-1 regulates myelin sheath thickness. Science 304:700–703

    Article  PubMed  CAS  Google Scholar 

  29. Taveggia C, Zanazzi G, Petrylak A, Yano H, Rosenbluth J, Einheber S, Xu X, Esper RM, Loeb JA, Shrager P, Chao MV, Falls DL, Role L, Salzer JL (2005) Neuregulin-1 type III determines the ensheathment fate of axons. Neuron 47:681–694

    Article  PubMed  CAS  Google Scholar 

  30. Zanazzi G, Einheber S, Westreich R, Hannocks MJ, Bedell-Hogan D, Marchionni MA, Salzer JL (2001) Glial growth factor/neuregulin inhibits Schwann cell myelination and induces demyelination. J Cell Biol 152:1289–1299

    Article  PubMed  CAS  Google Scholar 

  31. Huijbregts RP, Roth KA, Schmidt RE, Carroll SL (2003) Hypertrophic neuropathies and malignant peripheral nerve sheath tumors in transgenic mice overexpressing glial growth factor beta3 in myelinating Schwann cells. J Neurosci 23:7269–7280

    PubMed  CAS  Google Scholar 

  32. Canoll PD, Musacchio JM, Hardy R, Reynolds R, Marchionni MA, Salzer JL (1996) GGF/neuregulin is a neuronal signal that promotes the proliferation and survival and inhibits the differentiation of oligodendrocyte progenitors. Neuron 17:229–243

    Article  PubMed  CAS  Google Scholar 

  33. Milner R, Anderson HJ, Rippon RF, McKay JS, Franklin RJ, Marchionni MA, Reynolds R, Ffrench-Constant C (1997) Contrasting effects of mitogenic growth factors on oligodendrocyte precursor cell migration. Glia 19:85–90

    Article  PubMed  CAS  Google Scholar 

  34. Raabe TD, Suy S, Welcher A, DeVries GH (1997) Effect of neu differentiation factor isoforms on neonatal oligodendrocyte function. J Neurosci Res 50:755–768

    Article  PubMed  CAS  Google Scholar 

  35. Shi J, Marinovich A, Barres BA (1998) Purification and characterization of adult oligodendrocyte precursor cells from the rat optic nerve. J Neurosci 18:4627–4636

    PubMed  CAS  Google Scholar 

  36. Fernandez PA, Tang DG, Cheng L, Prochiantz A, Mudge AW, Raff MC (2000) Evidence that axon-derived neuregulin promotes oligodendrocyte survival in the developing rat optic nerve. Neuron 28:81–90

    Article  PubMed  CAS  Google Scholar 

  37. Calaora V, Rogister B, Bismuth K, Murray K, Brandt H, Leprince P, Marchionni M, Dubois-Dalcq M (2001) Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro. J Neurosci 21:4740–4751

    PubMed  CAS  Google Scholar 

  38. Wang Z, Colognato H, Ffrench-Constant C (2007) Contrasting effects of mitogenic growth factors on myelination in neuron-oligodendrocyte co-cultures. Glia 55:537–545

    Article  PubMed  Google Scholar 

  39. Roy K, Murtie JC, El-Khodor BF, Edgar N, Sardi SP, Hooks BM, Benoit-Marand M, Chen C, Moore H, O’Donnell P, Brunner D, Corfas G (2007) Loss of erbB signaling in oligodendrocytes alters myelin and dopaminergic function, a potential mechanism for neuropsychiatric disorders. Proc Natl Acad Sci U S A 104:8131–8136

    Article  PubMed  CAS  Google Scholar 

  40. Taveggia C, Thaker P, Petrylak A, Caporaso GL, Toews A, Falls DL, Einheber S, Salzer JL (2008) Type III neuregulin-1 promotes oligodendrocyte myelination. Glia 56:284–293

    Article  PubMed  Google Scholar 

  41. Brinkmann BG, Agarwal A, Sereda MW, Garratt AN, Muller T, Wende H, Stassart RM, Nawaz S, Humml C, Velanac V, Radyushkin K, Goebbels S, Fischer TM, Franklin RJ, Lai C, Ehrenreich H, Birchmeier C, Schwab MH, Nave KA (2008) Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system. Neuron 59:581–595

    Article  PubMed  CAS  Google Scholar 

  42. Prevot V, Cornea A, Mungenast A, Smiley G, Ojeda SR (2003) Activation of erbB-1 signaling in tanycytes of the median eminence stimulates transforming growth factor beta1 release via prostaglandin E2 production and induces cell plasticity. J Neurosci 23:10622–10632

    PubMed  CAS  Google Scholar 

  43. Prevot V, Lomniczi A, Corfas G, Ojeda SR (2005) erbB-1 and erbB-4 receptors act in concert to facilitate female sexual development and mature reproductive function. Endocrinology 146:1465–1472

    Article  PubMed  CAS  Google Scholar 

  44. Prevot V, Rio C, Cho GJ, Lomniczi A, Heger S, Neville CM, Rosenthal NA, Ojeda SR, Corfas G (2003) Normal female sexual development requires neuregulin-erbB receptor signaling in hypothalamic astrocytes. J Neurosci 23:230–239

    PubMed  CAS  Google Scholar 

  45. Sharif A, Duhem-Tonnelle V, Allet C, Baroncini M, Loyens A, Kerr-Conte J, Collier F, Blond S, Ojeda SR, Junier MP, Prevot V (2009) Differential erbB signaling in astrocytes from the cerebral cortex and the hypothalamus of the human brain. Glia 57:362–379

    Article  PubMed  Google Scholar 

  46. Calvo M, Zhu N, Tsantoulas C, Ma Z, Grist J, Loeb JA, Bennett DL (2010) Neuregulin-ErbB signaling promotes microglial proliferation and chemotaxis contributing to microgliosis and pain after peripheral nerve injury. J Neurosci 30:5437–5450

    Article  PubMed  CAS  Google Scholar 

  47. Lax I, Bellot F, Howk R, Ullrich A, Givol D, Schlessinger J (1989) Functional analysis of the ligand binding site of EGF-receptor utilizing chimeric chicken/human receptor molecules. EMBO J 8:421–427

    PubMed  CAS  Google Scholar 

  48. Summerfield AE, Hudnall AK, Lukas TJ, Guyer CA, Staros JV (1996) Identification of residues of the epidermal growth factor receptor proximal to residue 45 of bound epidermal growth factor. J Biol Chem 271:19656–19659

    Article  PubMed  CAS  Google Scholar 

  49. Garrett TP, McKern NM, Lou M, Elleman TC, Adams TE, Lovrecz GO, Zhu HJ, Walker F, Frenkel MJ, Hoyne PA, Jorissen RN, Nice EC, Burgess AW, Ward CW (2002) Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha. Cell 110:763–773

    Article  PubMed  CAS  Google Scholar 

  50. Ogiso H, Ishitani R, Nureki O, Fukai S, Yamanaka M, Kim JH, Saito K, Sakamoto A, Inoue M, Shirouzu M, Yokoyama S (2002) Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell 110:775–787

    Article  PubMed  CAS  Google Scholar 

  51. Plowman GD, Culouscou JM, Whitney GS, Green JM, Carlton GW, Foy L, Neubauer MG, Shoyab M (1993) Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci U S A 90:1746–1750

    Article  PubMed  CAS  Google Scholar 

  52. Culouscou JM, Plowman GD, Carlton GW, Green JM, Shoyab M (1993) Characterization of a breast cancer cell differentiation factor that specifically activates the HER4/p180erbB4 receptor. J Biol Chem 268:18407–18410

    PubMed  CAS  Google Scholar 

  53. Plowman GD, Green JM, Culouscou JM, Carlton GW, Rothwell VM, Buckley S (1993) Heregulin induces tyrosine phosphorylation of HER4/p180erbB4. Nature 366:473–475

    Article  PubMed  CAS  Google Scholar 

  54. Ferguson KM, Darling PJ, Mohan MJ, Macatee TL, Lemmon MA (2000) Extracellular domains drive homo- but not hetero-dimerization of erbB receptors. EMBO J 19:4632–4643

    Article  PubMed  CAS  Google Scholar 

  55. Mendrola JM, Berger MB, King MC, Lemmon MA (2002) The single transmembrane domains of ErbB receptors self-associate in cell membranes. J Biol Chem 277:4704–4712

    Article  PubMed  CAS  Google Scholar 

  56. Tzahar E, Waterman H, Chen X, Levkowitz G, Karunagaran D, Lavi S, Ratzkin BJ, Yarden Y (1996) A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol Cell Biol 16:5276–5287

    PubMed  CAS  Google Scholar 

  57. Graus-Porta D, Beerli RR, Daly JM, Hynes NE (1997) ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J 16:1647–1655

    Article  PubMed  CAS  Google Scholar 

  58. Sliwkowski MX, Schaefer G, Akita RW, Lofgren JA, Fitzpatrick VD, Nuijens A, Fendly BM, Cerione RA, Vandlen RL, Carraway KL III (1994) Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. J Biol Chem 269:14661–14665

    PubMed  CAS  Google Scholar 

  59. Carraway KL III, Cantley LC (1994) A neu acquaintance for erbB3 and erbB4: a role for receptor heterodimerization in growth signaling. Cell 78:5–8

    Article  PubMed  CAS  Google Scholar 

  60. Sawyer C, Hiles I, Page M, Crompton M, Dean C (1998) Two erbB-4 transcripts are expressed in normal breast and in most breast cancers. Oncogene 17:919–924

    Article  PubMed  CAS  Google Scholar 

  61. Kassis J, Moellinger J, Lo H, Greenberg NM, Kim HG, Wells A (1999) A role for phospholipase C-gamma-mediated signaling in tumor cell invasion. Clin Cancer Res 5:2251–2260

    PubMed  CAS  Google Scholar 

  62. Fedi P, Pierce JH, di Fiore PP, Kraus MH (1994) Efficient coupling with phosphatidylinositol 3-kinase, but not phospholipase C gamma or GTPase-activating protein, distinguishes ErbB-3 signaling from that of other ErbB/EGFR family members. Mol Cell Biol 14:492–500

    PubMed  CAS  Google Scholar 

  63. Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2:127–137

    Article  PubMed  CAS  Google Scholar 

  64. Olayioye MA, Neve RM, Lane HA, Hynes NE (2000) The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19:3159–3167

    Article  PubMed  CAS  Google Scholar 

  65. Tikhomirov O, Carpenter G (2004) Ligand-induced, p38-dependent apoptosis in cells expressing high levels of epidermal growth factor receptor and ErbB-2. J Biol Chem 279:12988–12996

    Article  PubMed  CAS  Google Scholar 

  66. Tzahar E, Yarden Y (1998) The ErbB-2/HER2 oncogenic receptor of adenocarcinomas: from orphanhood to multiple stromal ligands. Biochim Biophys Acta 1377:M25–M37

    PubMed  CAS  Google Scholar 

  67. Elenius K, Corfas G, Paul S, Choi CJ, Rio C, Plowman GD, Klagsbrun M (1997) A novel juxtamembrane domain isoform of HER4/ErbB4. Isoform-specific tissue distribution and differential processing in response to phorbol ester. J Biol Chem 272:26761–26768

    Article  PubMed  CAS  Google Scholar 

  68. Elenius K, Choi CJ, Paul S, Santiestevan E, Nishi E, Klagsbrun M (1999) Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase. Oncogene 18:2607–2615

    Article  PubMed  CAS  Google Scholar 

  69. Vecchi M, Carpenter G (1997) Constitutive proteolysis of the ErbB-4 receptor tyrosine kinase by a unique, sequential mechanism. J Cell Biol 139:995–1003

    Article  PubMed  CAS  Google Scholar 

  70. Rio C, Buxbaum JD, Peschon JJ, Corfas G (2000) Tumor necrosis factor-alpha-converting enzyme is required for cleavage of erbB4/HER4. J Biol Chem 275:10379–10387

    Article  PubMed  CAS  Google Scholar 

  71. Zhou W, Carpenter G (2000) Heregulin-dependent trafficking and cleavage of ErbB-4. J Biol Chem 275:34737–34743

    Article  PubMed  CAS  Google Scholar 

  72. Vecchi M, Baulida J, Carpenter G (1996) Selective cleavage of the heregulin receptor ErbB-4 by protein kinase C activation. J Biol Chem 271:18989–18995

    Article  PubMed  CAS  Google Scholar 

  73. Ni CY, Murphy MP, Golde TE, Carpenter G (2001) gamma-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science 294:2179–2181

    Article  PubMed  CAS  Google Scholar 

  74. Lee HJ, Jung KM, Huang YZ, Bennett LB, Lee JS, Mei L, Kim TW (2002) Presenilin-dependent gamma-secretase-like intramembrane cleavage of ErbB4. J Biol Chem 277:6318–6323

    Article  PubMed  CAS  Google Scholar 

  75. Sardi SP, Murtie J, Koirala S, Patten BA, Corfas G (2006) Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain. Cell 127:185–197

    Article  PubMed  CAS  Google Scholar 

  76. Naresh A, Long W, Vidal GA, Wimley WC, Marrero L, Sartor CI, Tovey S, Cooke TG, Bartlett JM, Jones FE (2006) The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein promoting apoptosis of breast cancer cells. Cancer Res 66:6412–6420

    Article  PubMed  CAS  Google Scholar 

  77. Naresh A, Thor AD, Edgerton SM, Torkko KC, Kumar R, Jones FE (2008) The HER4/4ICD estrogen receptor coactivator and BH3-only protein is an effector of tamoxifen-induced apoptosis. Cancer Res 68:6387–6395

    Article  PubMed  CAS  Google Scholar 

  78. Schroeder JA, Thompson MC, Gardner MM, Gendler SJ (2001) Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland. J Biol Chem 276:13057–13064

    Article  PubMed  CAS  Google Scholar 

  79. Yu WH, Woessner JF Jr, McNeish JD, Stamenkovic I (2002) CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. Genes Dev 16:307–323

    Article  PubMed  CAS  Google Scholar 

  80. Eckert JM, Byer SJ, Clodfelder-Miller BJ, Carroll SL (2009) Neuregulin-1 beta and neuregulin-1 alpha differentially affect the migration and invasion of malignant peripheral nerve sheath tumor cells. Glia 57:1501–1520

    Article  PubMed  Google Scholar 

  81. Carraway KL, Theodoropoulos G, Kozloski GA, Carothers Carraway CA (2009) Muc4/MUC4 functions and regulation in cancer. Future Oncol 5:1631–1640

    Article  PubMed  CAS  Google Scholar 

  82. Mei L, Xiong WC (2008) Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci 9:437–452

    Article  PubMed  CAS  Google Scholar 

  83. Holmes WE, Sliwkowski MX, Akita RW, Henzel WJ, Lee J, Park JW, Yansura D, Abadi N, Raab H, Lewis GD et al (1992) Identification of heregulin, a specific activator of p185erbB2. Science 256:1205–1210

    Article  PubMed  CAS  Google Scholar 

  84. Hu X, Hicks CW, He W, Wong P, Macklin WB, Trapp BD, Yan R (2006) Bace1 modulates myelination in the central and peripheral nervous system. Nat Neurosci 9:1520–1525

    Article  PubMed  CAS  Google Scholar 

  85. Willem M, Garratt AN, Novak B, Citron M, Kaufmann S, Rittger A, DeStrooper B, Saftig P, Birchmeier C, Haass C (2006) Control of peripheral nerve myelination by the beta-secretase BACE1. Science 314:664–666

    Article  PubMed  CAS  Google Scholar 

  86. Loeb JA, Susanto ET, Fischbach GD (1998) The neuregulin precursor proARIA is processed to ARIA after expression on the cell surface by a protein kinase C-enhanced mechanism. Mol Cell Neurosci 11:77–91

    Article  PubMed  CAS  Google Scholar 

  87. Montero JC, Rodriguez-Barrueco R, Yuste L, Juanes PP, Borges J, Esparis-Ogando A, Pandiella A (2007) The extracellular linker of pro-neuregulin-alpha2c is required for efficient sorting and juxtacrine function. Mol Biol Cell 18:380–393

    Article  PubMed  CAS  Google Scholar 

  88. Yokozeki T, Wakatsuki S, Hatsuzawa K, Black RA, Wada I, Sehara-Fujisawa A (2007) Meltrin beta (ADAM19) mediates ectodomain shedding of Neuregulin beta1 in the Golgi apparatus: fluorescence correlation spectroscopic observation of the dynamics of ectodomain shedding in living cells. Genes Cells 12:329–343

    Article  PubMed  CAS  Google Scholar 

  89. Buonanno A, Fischbach GD (2001) Neuregulin and ErbB receptor signaling pathways in the nervous system. Curr Opin Neurobiol 11:287–296

    Article  PubMed  CAS  Google Scholar 

  90. Bao J, Wolpowitz D, Role LW, Talmage DA (2003) Back signaling by the Nrg-1 intracellular domain. J Cell Biol 161:1133–1141

    Article  PubMed  CAS  Google Scholar 

  91. Bao J, Lin H, Ouyang Y, Lei D, Osman A, Kim TW, Mei L, Dai P, Ohlemiller KK, Ambron RT (2004) Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos. Nat Neurosci 7:1250–1258

    Article  PubMed  CAS  Google Scholar 

  92. Hancock ML, Canetta SE, Role LW, Talmage DA (2008) Presynaptic type III neuregulin1-ErbB signaling targets {alpha}7 nicotinic acetylcholine receptors to axons. J Cell Biol 181:511–521

    Article  PubMed  CAS  Google Scholar 

  93. Crovello CS, Lai C, Cantley LC, Carraway KL III (1998) Differential signaling by the epidermal growth factor-like growth factors neuregulin-1 and neuregulin-2. J Biol Chem 273:26954–26961

    Article  PubMed  CAS  Google Scholar 

  94. Frohnert PW, Stonecypher MS, Carroll SL (2003) Lysophosphatidic acid promotes the proliferation of adult Schwann cells isolated from axotomized sciatic nerve. J Neuropathol Exp Neurol 62:520–529

    PubMed  CAS  Google Scholar 

  95. Frohnert PW, Stonecypher MS, Carroll SL (2003) Constitutive activation of the neuregulin-1/ErbB receptor signaling pathway is essential for the proliferation of a neoplastic Schwann cell line. Glia 43:104–118

    Article  PubMed  Google Scholar 

  96. Shin KJ, Wall EA, Zavzavadjian JR, Santat LA, Liu J, Hwang JI, Rebres R, Roach T, Seaman W, Simon MI, Fraser ID (2006) A single lentiviral vector platform for microRNA-based conditional RNA interference and coordinated transgene expression. Proc Natl Acad Sci U S A 103:13759–13764

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The development of the experimental protocols described in this chapter was supported by grants from the National Institute of Neurological Diseases and Stroke (R01 NS048353 to S.L.C.; F30 NS063626 to N.M.B.), the National Cancer Institute (R01 CA122804 to S.L.C.; R01 CA134773 to Kevin A. Roth and S.L.C.), and the Department of Defense (X81XWH-09-1-0086 to S.L.C.). L.T.P. was supported in part by a grant to the University of Alabama at Birmingham from the Howard Hughes Medical Institute through the Med into Grad Initiative. We thank the Alabama Neuroscience Blueprint Core Center (P30 NS57098) and the UAB Neuroscience Core Center (P30 NS47466) for technical assistance with studies from our laboratory that are described in this chapter. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Defense.

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Correspondence to Steven L. Carroll .

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Brossier, N.M., Byer, S.J., Peavler, L.T., Carroll, S.L. (2012). ErbB Membrane Tyrosine Kinase Receptors: Analyzing Migration in a Highly Complex Signaling System. In: Mukai, H. (eds) Protein Kinase Technologies. Neuromethods, vol 68. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-824-5_7

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  • DOI: https://doi.org/10.1007/978-1-61779-824-5_7

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