The ErbB4 receptor in fetal rat lung fibroblasts and epithelial type II cells.
Journal: 2007/September - Biochimica et Biophysica Acta - General Subjects
ISSN: 0006-3002
Abstract:
ErbB receptors are important regulators of fetal organ development, including the fetal lung. They exhibit diversity in signaling potential, acting through homo- and heterodimers to cause different biological responses. We hypothesized that ErbB receptors show cell-specific and stimuli-specific activation, heterodimerization, and cellular localization patterns in fetal lung. We investigated this using immunoblotting, co-immunoprecipitation, and confocal microscopy in primary isolated E19 fetal rat lung fibroblasts and epithelial type II cells, stimulated with epidermal growth factor, transforming growth factor alpha, neuregulin 1beta, or treated with conditioned medium (CM) from the respective other cell type. Fetal type II cells expressed significantly more ErbB1, ErbB2, and ErbB3 protein than fibroblasts. ErbB4 was consistently identified by co-immunoprecipitation of all other ErbB receptors in both cell types independent of the treatments. Downregulation of ErbB4 in fibroblasts initiated cell-cell communication that stimulated surfactant phospholipid synthesis in type II cells. Confocal microscopy in type II cells revealed nuclear localization of all receptors, most prominently for ErbB4. Neuregulin treatment resulted in relocation to the extra-nuclear cytoplasmic region, which was distinct from fibroblast CM treatment which led to nuclear localization of ErbB4 and ErbB2, inducing co-localization of both receptors. We speculate that ErbB4 plays a prominent role in fetal lung mesenchyme-epithelial communication.
Relations:
Content
Citations
(10)
References
(44)
Chemicals
(3)
Genes
(4)
Organisms
(3)
Processes
(4)
Anatomy
(3)
Similar articles
Articles by the same authors
Discussion board
Biochim Biophys Acta 1772(7): 737-747

The ErbB4 Receptor in Fetal Rat Lung Fibroblasts and Epithelial Type II Cells

Newborn Medicine, Department of Pediatrics, Floating Hospital for Children, Tufts-New England Medical Center, Boston, MA 02111, USA
Pediatric Pulmonology and Neonatology, Department of Pediatrics, Hannover Medical School, 30625 Hannover, Germany
University of Applied Sciences Lausitz, Senftenberg, Germany
Corresponding author: Washa Liu, MD, Newborn Medicine, Department of Pediatrics, Floating Hospital for Children, Tufts-New England Medical Center, Boston, MA 02111, USA, Tel: (617) 636 5054, Fax: (617) 636 4233, Email: gro.cmen-stfut@2uilw
Publisher's Disclaimer

Abstract

ErbB receptors are important regulators of fetal organ development, including the fetal lung. They exhibit diversity in signaling potential, acting through homo- and heterodimers to cause different biological responses. We hypothesized that ErbB receptors show cell-specific and stimuli-specific, activation, heterodimerization, and cellular localization patterns in fetal lung. We investigated this using immunoblotting, co-immunoprecipitation, and confocal microscopy in primary isolated E19 fetal rat lung fibroblasts and epithelial type II cells, stimulated with epidermal growth factor, transforming growth factor α, neuregulin 1β or treated with conditioned medium (CM) from the respective other cell type. Fetal type II cells expressed significantly more ErbB1, ErbB2, and ErbB3 protein than fibroblasts. ErbB4 was consistently identified by co-immunoprecipitation of all other ErbB receptors in both cell types independent of the treatments. Down regulation of ErbB4 in fibroblasts initiated cell-cell communication that stimulated surfactant phospholipid synthesis in type II cells. Confocal microscopy in type II cells revealed nuclear localization of all receptors, most prominently for ErbB4. Neuregulin treatment resulted in relocation to the extra-nuclear cytoplasmic region, which was distinct from fibroblast CM treatment which led to nuclear localization of ErbB4 and ErbB2, inducing co-localization of both receptors. We speculate that ErbB4 plays a prominent role in fetal lung mesenchyme-epithelial communication.

Keywords: Neuregulin, epidermal growth factor, transforming growth factor α, conditioned medium, lung development
Abstract

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Footnotes

References

  • 1. Alroy I, Yarden YThe ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions. FEBS Lett. 1997;410:83.[PubMed][Google Scholar]
  • 2. Caniggia I, Tseu I, Han RN, Smith BT, Tanswell K, Post MSpatial and temporal differences in fibroblast behavior in fetal rat lung. Am J Physiol. 1991;261:L424–L433.[PubMed][Google Scholar]
  • 3. Carpenter GErbB-4: mechanism of action and biology. Exp Cell Res. 2003;284:66.[PubMed][Google Scholar]
  • 4. Carraway KL, III, Burden SJNeuregulins and their receptors. Curr Opin Neurobiol. 1995;5:606.[PubMed][Google Scholar]
  • 5. Carraway KL, III, Rossi EA, Komatsu M, Price-Schiavi SA, Huang D, Guy PM, Carvajal ME, Fregien N, Carraway CA, Carraway KLAn intramembrane modulator of the ErbB2 receptor tyrosine kinase that potentiates neuregulin signaling. J Biol Chem. 1999;274:5263.[PubMed][Google Scholar]
  • 6. Chattopadhyay A, Vecchi M, Ji Q, Mernaugh R, Carpenter GThe role of individual SH2 domains in mediating association of phospholipase C-gamma1 with the activated EGF receptor. J Biol Chem. 1999;274:26091.[PubMed][Google Scholar]
  • 7. Cho HS, Leahy DJStructure of the extracellular region of HER3 reveals an interdomain tether. Science. 2002;297:1330.[PubMed][Google Scholar]
  • 8. Dammann CE, Nielsen HC, Carraway KL., III Role of neuregulin-1 beta in the developing lung. Am J Respir Crit Care Med. 2003;167:1711.[PubMed]
  • 9. Ebner R, Derynck REpidermal growth factor and transforming growth factor-alpha: differential intracellular routing and processing of ligand-receptor complexes. Cell Regul. 1991;2:599.[Google Scholar]
  • 10. Fitzpatrick VD, Pisacane PI, Vandlen RL, Sliwkowski MXFormation of a high affinity heregulin binding site using the soluble extracellular domains of ErbB2 with ErbB3 or ErbB4. FEBS Lett. 1998;431:102.[PubMed][Google Scholar]
  • 11. 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 CWCrystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha. Cell. 2002;110:763.[PubMed][Google Scholar]
  • 12. Gassmann M, Casagranda F, Orioli D, Simon H, Lai C, Klein R, Lemke GAberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature. 1995;378:390.[PubMed][Google Scholar]
  • 13. Graus-Porta D, Beerli RR, Daly JM, Hynes NEErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J. 1997;16:1647.[Google Scholar]
  • 14. Hashimoto Y, Katayama H, Kiyokawa E, Ota S, Kurata T, Gotoh N, Otsuka N, Shibata M, Matsuda MPhosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor. J Biol Chem. 1998;273:17186.[PubMed][Google Scholar]
  • 15. Huang GC, Ouyang X, Epstein RJProxy activation of protein ErbB2 by heterologous ligands implies a heterotetrameric mode of receptor tyrosine kinase interaction. Biochem J. 1998;331( Pt 1):113.[Google Scholar]
  • 16. Ji QS, Chattopadhyay A, Vecchi M, Carpenter GPhysiological requirement for both SH2 domains for phospholipase C-gamma1 function and interaction with platelet-derived growth factor receptors. Mol Cell Biol. 1999;19:4961.[Google Scholar]
  • 17. Klapper LN, Glathe S, Vaisman N, Hynes NE, Andrews GC, Sela M, Yarden YThe ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci U S A. 1999;96:4995.[Google Scholar]
  • 18. Lee KF, Simon H, Chen H, Bates B, Hung MC, Hauser CRequirement for neuregulin receptor erbB2 in neural and cardiac development. Nature. 1995;378:394.[PubMed][Google Scholar]
  • 19. Lin SY, Makino K, Xia W, Matin A, Wen Y, Kwong KY, Bourguignon L, Hung MCNuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol. 2001;3:802.[PubMed][Google Scholar]
  • 20. LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJProtein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265.[PubMed][Google Scholar]
  • 21. Miettinen PJ, Berger JE, Meneses J, Phung Y, Pedersen RA, Werb Z, Derynck REpithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature. 1995;376:337.[PubMed][Google Scholar]
  • 22. Murray S, Pham L, Dammann CEL, Nielsen HCInhibition of ErbB Receptor Function in Murine and Human Pulmonary Epithelial Cells. 2004[PubMed]
  • 23. Ni CY, Murphy MP, Golde TE, Carpenter Ggamma -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science. 2001;294:2179.[PubMed][Google Scholar]
  • 24. Nielsen HCEpidermal growth factor influences the developmental clock regulating maturation of the fetal lung fibroblast. Biochim Biophys Acta. 1989;1012:201.[PubMed][Google Scholar]
  • 25. Nielsen HC, Martin A, Volpe MV, Hatzis D, Vosatka RJGrowth factor control of growth and epithelial differentiation in embryonic lungs. Biochem Mol Med. 1997;60:38.[PubMed][Google Scholar]
  • 26. Nielsen HC, Torday JSAnatomy of fetal rabbit gonads and the sexing of fetal rabbits. Lab Anim. 1983;17:148.[PubMed][Google Scholar]
  • 27. Offterdinger M, Schofer C, Weipoltshammer K, Grunt TWc-erbB-3: a nuclear protein in mammary epithelial cells. J Cell Biol. 2002;157:929.[Google Scholar]
  • 28. Olski TM, Noegel AA, Korenbaum EParvin, a 42 kDa focal adhesion protein, related to the alpha-actinin superfamily. J Cell Sci. 2001;114:525.[PubMed][Google Scholar]
  • 29. Post M, Smith BTHistochemical and immunocytochemical identification of alveolar type II epithelial cells isolated from fetal rat lung. Am Rev Respir Dis. 1988;137:525.[PubMed][Google Scholar]
  • 30. Prevot V, Lomniczi A, Corfas G, Ojeda SRerbB-1 and erbB-4 receptors act in concert to facilitate female sexual development and mature reproductive function. Endocrinology. 2005;146:1465.[PubMed][Google Scholar]
  • 31. Riese DJ, Komurasaki T, Plowman GD, Stern DFActivation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. J Biol Chem. 1998;273:11288.[PubMed][Google Scholar]
  • 32. Riese DJ, Stern DFSpecificity within the EGF family/ErbB receptor family signaling network. Bioessays. 1998;20:41.[PubMed][Google Scholar]
  • 33. Riethmacher D, Sonnenberg-Riethmacher E, Brinkmann V, Yamaai T, Lewin GR, Birchmeier CSevere neuropathies in mice with targeted mutations in the ErbB3 receptor. Nature. 1997;389:725.[PubMed][Google Scholar]
  • 34. Rosenblum DA, Volpe MV, Dammann CE, Lo YS, Thompson JF, Nielsen HCExpression and activity of epidermal growth factor receptor in late fetal rat lung is cell- and sex-specific. Exp Cell Res. 1998;239:69.[PubMed][Google Scholar]
  • 35. Ruocco S, Lallemand A, Tournier JM, Gaillard DExpression and localization of epidermal growth factor, transforming growth factor-alpha, and localization of their common receptor in fetal human lung development. Pediatr Res. 1996;39:448.[PubMed][Google Scholar]
  • 36. Saito Y, Haendeler J, Hojo Y, Yamamoto K, Berk BCReceptor heterodimerization: essential mechanism for platelet-derived growth factor-induced epidermal growth factor receptor transactivation. Mol Cell Biol. 2001;21:6387.[Google Scholar]
  • 37. Schultz CJ, Torres E, Londos C, Torday JSRole of adipocyte differentiation-related protein in surfactant phospholipid synthesis by type II cells. Am J Physiol Lung Cell Mol Physiol. 2002;283:L288–L296.[PubMed][Google Scholar]
  • 38. Shelly M, Pinkas-Kramarski R, Guarino BC, Waterman H, Wang LM, Lyass L, Alimandi M, Kuo A, Bacus SS, Pierce JH, Andrews GC, Yarden YEpiregulin is a potent pan-ErbB ligand that preferentially activates heterodimeric receptor complexes. J Biol Chem. 1998;273:10496.[PubMed][Google Scholar]
  • 39. Sliwkowski MX, Schaefer G, Akita RW, Lofgren JA, Fitzpatrick VD, Nuijens A, Fendly BM, Cerione RA, Vandlen RL, Carraway KL., III Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. J Biol Chem. 1994;269:14661.[PubMed]
  • 40. Smith BTLung maturation in the fetal rat: acceleration by injection of fibroblast-pneumonocyte factor. Science. 1979;204:1094.[PubMed][Google Scholar]
  • 41. Sweeney C, Fambrough D, Huard C, Diamonti AJ, Lander ES, Cantley LC, Carraway KL., III Growth factor-specific signaling pathway stimulation and gene expression mediated by ErbB receptors. J Biol Chem. 2001;276:22685.[PubMed]
  • 42. Sweeney C, Miller JK, Shattuck DL, Carraway KL., III ErbB receptor negative regulatory mechanisms: implications in cancer. J Mammary Gland Biol Neoplasia. 2006;11:89.[PubMed]
  • 43. Torday JS, Torres E, Rehan VKThe role of fibroblast transdifferentiation in lung epithelial cell proliferation, differentiation, and repair in vitro. Pediatr Pathol Mol Med. 2003;22:189.[PubMed][Google Scholar]
  • 44. Williams CC, Allison JG, Vidal GA, Burow ME, Beckman BS, Marrero L, Jones FEThe ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone. J Cell Biol. 2004;167:469.[Google Scholar]
  • 45. Zscheppang K, Liu W, Volpe MV, Nielsen HC, Dammann CELErbB4 Regulates Fetal Surfactant Synthesis. Proc Am Thor Soc. 2006;3:A672.[PubMed][Google Scholar]
  • 46. Zscheppang K, Korenbaum E, Bueter W, Ramadurai SM, Nielsen HC, Dammann CEErbB receptor dimerization, localization, and co-localization in mouse lung type II epithelial cells. Pediatr Pulmonol. 2006;41:1205.[PubMed][Google Scholar]
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.