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
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
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
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
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
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
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
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
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
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
Gerecke KM, Wyss JM, Carroll SL (2004) Neuregulin-1beta induces neurite extension and arborization in cultured hippocampal neurons. Mol Cell Neurosci 27:379–393
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
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
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
Ozaki M, Sasner M, Yano R, Lu HS, Buonanno A (1997) Neuregulin-beta induces expression of an NMDA-receptor subunit. Nature 390:691–694
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Plowman GD, Green JM, Culouscou JM, Carlton GW, Rothwell VM, Buckley S (1993) Heregulin induces tyrosine phosphorylation of HER4/p180erbB4. Nature 366:473–475
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
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
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
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
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
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
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
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
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
Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2:127–137
Olayioye MA, Neve RM, Lane HA, Hynes NE (2000) The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19:3159–3167
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
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
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
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
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
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
Zhou W, Carpenter G (2000) Heregulin-dependent trafficking and cleavage of ErbB-4. J Biol Chem 275:34737–34743
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
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
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
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
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
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
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
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
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
Carraway KL, Theodoropoulos G, Kozloski GA, Carothers Carraway CA (2009) Muc4/MUC4 functions and regulation in cancer. Future Oncol 5:1631–1640
Mei L, Xiong WC (2008) Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci 9:437–452
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
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
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
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
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
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
Buonanno A, Fischbach GD (2001) Neuregulin and ErbB receptor signaling pathways in the nervous system. Curr Opin Neurobiol 11:287–296
Bao J, Wolpowitz D, Role LW, Talmage DA (2003) Back signaling by the Nrg-1 intracellular domain. J Cell Biol 161:1133–1141
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
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
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
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
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
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
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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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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