The intracellular signal transduction mechanism of interleukin 5 in eosinophils: the involvement of lyn tyrosine kinase and the Ras-Raf-1- MEK-microtubule-associated protein kinase pathway

doi:10.1084/jem.181.5.1827

This Article

Full Text (PDF)

Alert me when this article is cited

Citation Map

Services

Email this article

Similar articles in this journal

Similar articles in PubMed

Alert me to new content in the JEM

Download to citation manager

Citing Articles

Citing Articles via HighWire

Citing Articles via CrossRef

Citing Articles via Google Scholar

Google Scholar

Articles by Pazdrak, K.

Articles by Alam, R.

Search for Related Content

PubMed

PubMed Citation

Articles by Pazdrak, K.

Articles by Alam, R.

Pubmed/NCBI databases

Substance via MeSH

Social Bookmarking

What's this?

ARTICLES

The intracellular signal transduction mechanism of interleukin 5 in eosinophils: the involvement of lyn tyrosine kinase and the Ras-Raf-1- MEK-microtubule-associated protein kinase pathway

K Pazdrak, D Schreiber, P Forsythe, L Justement and R Alam
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0762, USA.

Interleukin 5 (IL-5) regulates the growth and function of eosinophils. The objective of this study was to investigate the intracellular signal transduction mechanism of IL-5 in eosinophils. Purified eosinophils were stimulated with IL-5, and the involvement of various kinases was investigated by immunoblotting, immune complex kinase assay, and in situ denatured/renatured kinase assay. We found that IL-5 induced tyrosine phosphorylation and activation of a number of kinases. Two species of lyn kinases (53 and 56 kD) were present in eosinophils. Both forms were Tyr-phosphorylated and activated rapidly within 1 min. Further, lyn kinase was physically associated with the IL-5 beta receptor in eosinophils. Ras was studied by immunoprecipitation followed by thin-layer chromatography. Ras bound higher quantities of [alpha-32P]guanosine 5'triphosphate upon stimulation with IL-5. Raf-1 kinase showed increased Tyr phosphorylation on immunoblotting and increased activity in the immune complex kinase assay. Two species of MEK (MAP or Erk kinase) (41 and 45 kD) were identified in eosinophils, which underwent autophosphorylation upon stimulation. Microtubule- associated protein (MAP) kinase (p44) was Tyr-phosphorylated on immunoblotting and had increased activity in the immune-complex kinase assay. MAP kinases were also studied after metabolic radiolabeling of the cells with [32P]orthophosphates. IL-5 stimulated phosphorylation of MAP kinases in situ. Thus, we have delineated major components of an important signaling pathway in eosinophils. We believe that one of the signals generated by IL-5 receptor activation is propagated through the lyn-Ras-Raf-1-MEK-MAP kinase pathway.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Goplen, N., Gorska, M. M., Stafford, S. J., Rozario, S., Guo, L., Liang, Q., Alam, R. (2008). A Phosphosite Screen Identifies Autocrine TGF-{beta}-Driven Activation of Protein Kinase R as a Survival-Limiting Factor for Eosinophils. J. Immunol. 180: 4256-4264 [Abstract] [Full Text]
Norris, H. H., Peterson, M. E., Stebbins, C. C., McConchie, B. W., Bundoc, V. G., Trivedi, S., Hodges, M. G., Anthony, R. M., Urban, J. F. Jr, Long, E. O., Keane-Myers, A. M. (2007). Inhibitory receptor gp49B regulates eosinophil infiltration during allergic inflammation. J. Leukoc. Biol. 82: 1531-1541 [Abstract] [Full Text]
Gorska, M. M., Cen, O., Liang, Q., Stafford, S. J., Alam, R. (2006). Differential Regulation of Interleukin 5-stimulated Signaling Pathways by Dynamin. J. Biol. Chem. 281: 14429-14439 [Abstract] [Full Text]
Munitz, A., Bachelet, I., Eliashar, R., Moretta, A., Moretta, L., Levi-Schaffer, F. (2006). The inhibitory receptor IRp60 (CD300a) suppresses the effects of IL-5, GM-CSF, and eotaxin on human peripheral blood eosinophils. Blood 107: 1996-2003 [Abstract] [Full Text]
Beavitt, S.-J. E., Harder, K. W., Kemp, J. M., Jones, J., Quilici, C., Casagranda, F., Lam, E., Turner, D., Brennan, S., Sly, P. D., Tarlinton, D. M., Anderson, G. P., Hibbs, M. L. (2005). Lyn-Deficient Mice Develop Severe, Persistent Asthma: Lyn Is a Critical Negative Regulator of Th2 Immunity. J. Immunol. 175: 1867-1875 [Abstract] [Full Text]
Inoue, H., Kato, R., Fukuyama, S., Nonami, A., Taniguchi, K., Matsumoto, K., Nakano, T., Tsuda, M., Matsumura, M., Kubo, M., Ishikawa, F., Moon, B.-g., Takatsu, K., Nakanishi, Y., Yoshimura, A. (2005). Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness. J. Exp. Med. 201: 73-82 [Abstract] [Full Text]
Gregory, B., Kirchem, A., Phipps, S., Gevaert, P., Pridgeon, C., Rankin, S. M., Robinson, D. S. (2003). Differential Regulation of Human Eosinophil IL-3, IL-5, and GM-CSF Receptor {alpha}-Chain Expression by Cytokines: IL-3, IL-5, and GM-CSF Down-Regulate IL-5 Receptor {alpha} Expression with Loss of IL-5 Responsiveness, but Up-Regulate IL-3 Receptor {alpha} Expression . J. Immunol. 170: 5359-5366 [Abstract] [Full Text]
Cen, O., Gorska, M. M., Stafford, S. J., Sur, S., Alam, R. (2003). Identification of UNC119 as a Novel Activator of SRC-type Tyrosine Kinases. J. Biol. Chem. 278: 8837-8845 [Abstract] [Full Text]
Buitenhuis, M., Baltus, B., Lammers, J.-W. J., Coffer, P. J., Koenderman, L. (2003). Signal transducer and activator of transcription 5a (STAT5a) is required for eosinophil differentiation of human cord blood-derived CD34+ cells. Blood 101: 134-142 [Abstract] [Full Text]
Zangrilli, J. G. (2002). Regulation of Eosinophil Viability by Cytokines. Am. J. Respir. Cell Mol. Bio. 26: 388-390 [Full Text]
Ishikawa, H., Tsuyama, N., Abroun, S., Liu, S., Li, F.-J., Taniguchi, O., Kawano, M. M. (2002). Requirements of src family kinase activity associated with CD45 for myeloma cell proliferation by interleukin-6. Blood 99: 2172-2178 [Abstract] [Full Text]
Stafford, S., Lowell, C., Sur, S., Alam, R. (2002). Lyn Tyrosine Kinase Is Important for IL-5-Stimulated Eosinophil Differentiation. J. Immunol. 168: 1978-1983 [Abstract] [Full Text]
Hall, D. J., Cui, J., Bates, M. E., Stout, B. A., Koenderman, L., Coffer, P. J., Bertics, P. J. (2001). Transduction of a dominant-negative H-Ras into human eosinophils attenuates extracellular signal-regulated kinase activation and interleukin-5-mediated cell viability. Blood 98: 2014-2021 [Abstract] [Full Text]
Suzuki, T., Kiyokawa, N., Taguchi, T., Sekino, T., Katagiri, Y. U., Fujimoto, J. (2001). CD24 Induces Apoptosis in Human B Cells Via the Glycolipid-Enriched Membrane Domains/Rafts-Mediated Signaling System. J. Immunol. 166: 5567-5577 [Abstract] [Full Text]
Lach-Trifilieff, E., Menear, K., Schweighoffer, E., Tybulewicz, V. L. J., Walker, C. (2000). Syk-deficient eosinophils show normal interleukin-5-mediated differentiation, maturation, and survival but no longer respond to Fcgamma R activation. Blood 96: 2506-2510 [Abstract] [Full Text]
Adachi, T., Choudhury, B. K., Stafford, S., Sur, S., Alam, R. (2000). The Differential Role of Extracellular Signal-Regulated Kinases and p38 Mitogen-Activated Protein Kinase in Eosinophil Functions. J. Immunol. 165: 2198-2204 [Abstract] [Full Text]
ERJEFÄLT, J. S., PERSSON, C. G. A. (2000). New Aspects of Degranulation and Fates of Airway Mucosal Eosinophils. Am. J. Respir. Crit. Care Med. 161: 2074-2085 [Full Text]
Bates, M. E., Green, V. L., Bertics, P. J. (2000). ERK1 and ERK2 Activation by Chemotactic Factors in Human Eosinophils Is Interleukin 5-dependent and Contributes to Leukotriene C4 Biosynthesis. J. Biol. Chem. 275: 10968-10975 [Abstract] [Full Text]
Kampen, G. T., Stafford, S., Adachi, T., Jinquan, T., Quan, S., Grant, J. A., Skov, P. S., Poulsen, L. K., Alam, R. (2000). Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases. Blood 95: 1911-1917 [Abstract] [Full Text]
Tavernier, J., Van der Heyden, J., Verhee, A., Brusselle, G., Van Ostade, X., Vandekerckhove, J., North, J., Rankin, S. M., Kay, A. B., Robinson, D. S. (2000). Interleukin 5 regulates the isoform expression of its own receptor alpha -subunit. Blood 95: 1600-1607 [Abstract] [Full Text]
Kankaanranta, H., De Souza, P. M., Barnes, P. J., Salmon, M., Giembycz, M. A., Lindsay, M. A. (1999). SB 203580, an Inhibitor of p38 Mitogen-Activated Protein Kinase, Enhances Constitutive Apoptosis of Cytokine-Deprived Human Eosinophils. J. Pharmacol. Exp. Ther. 290: 621-628 [Abstract] [Full Text]
Evans, D. J., Lindsay, M. A., Webb, B. L. J., Kankaanranta, H., Giembycz, M. A., O'Connor, B. J., Barnes, P. J. (1999). Expression and activation of protein kinase C-zeta in eosinophils after allergen challenge. Am. J. Physiol. Lung Cell. Mol. Physiol. 277: L233-L239 [Abstract] [Full Text]
Adachi, T., Stafford, S., Sur, S., Alam, R. (1999). A Novel Lyn-Binding Peptide Inhibitor Blocks Eosinophil Differentiation, Survival, and Airway Eosinophilic Inflammation1, 2. J. Immunol. 163: 939-946 [Abstract] [Full Text]
Giembycz, M. A., Lindsay, M. A. (1999). Pharmacology of the Eosinophil. Pharmacol. Rev. 51: 213-340 [Abstract] [Full Text]
Gardiner, E. E., D'Souza, S. E. (1999). Sequences within Fibrinogen and Intercellular Adhesion Molecule-1 (ICAM-1) Modulate Signals Required for Mitogenesis. J. Biol. Chem. 274: 11930-11936 [Abstract] [Full Text]
Adachi, T., Pazdrak, K., Stafford, S., Alam, R. (1999). The Mapping of the Lyn Kinase Binding Site of the Common {beta} Subunit of IL-3/Granulocyte-Macrophage Colony- Stimulating Factor/IL-5 Receptor. J. Immunol. 162: 1496-1501 [Abstract] [Full Text]
Corey, S. J., Anderson, S. M. (1999). Src-Related Protein Tyrosine Kinases in Hematopoiesis. Blood 93: 1-14 [Full Text]
Bracke, M., Coffer, P. J., Lammers, J.-W. J., Koenderman, L. (1998). Analysis of Signal Transduction Pathways Regulating Cytokine-Mediated Fc Receptor Activation on Human Eosinophils. J. Immunol. 161: 6768-6774 [Abstract] [Full Text]
Palframan, R. T., Collins, P. D., Severs, N. J., Rothery, S., Williams, T. J., Rankin, S. M. (1998). Mechanisms of Acute Eosinophil Mobilization from the Bone Marrow Stimulated by Interleukin 5: The Role of Specific Adhesion Molecules and Phosphatidylinositol 3-Kinase. J. Exp. Med. 188: 1621-1632 [Abstract] [Full Text]
Adachi, T., Alam, R. (1998). The mechanism of IL-5 signal transduction. Am. J. Physiol. Cell Physiol. 275: C623-C633 [Abstract] [Full Text]
Pazdrak, K., Olszewska-Pazdrak, B., Stafford, S., Garofalo, R. P., Alam, R. (1998). Lyn, Jak2, and Raf-1 Kinases Are Critical for the Antiapoptotic Effect of Interleukin 5,�whereas only Raf-1 Kinase Is Essential for Eosinophil Activation and Degranulation. J. Exp. Med. 188: 421-429 [Abstract] [Full Text]
Simon, H.-U., Yousefi, S., Dibbert, B., Hebestreit, H., Weber, M., Branch, D. R., Blaser, K., Levi-Schaffer, F., Anderson, G. P. (1998). Role for Tyrosine Phosphorylation and Lyn Tyrosine Kinase in Fas Receptor-Mediated Apoptosis in Eosinophils. Blood 92: 547-557 [Abstract] [Full Text]
Chin, H., Arai, A., Wakao, H., Kamiyama, R., Miyasaka, N., Miura, O. (1998). Lyn Physically Associates With the Erythropoietin Receptor and May Play a Role in Activation of the Stat5 Pathway. Blood 91: 3734-3745 [Abstract] [Full Text]
Okada, S., Hagan, J. B., Kato, M., Bankers-Fulbright, J. L., Hunt, L. W., Gleich, G. J., Kita, H. (1998). Lidocaine and its Analogues Inhibit IL-5-Mediated Survival and Activation of Human Eosinophils. J. Immunol. 160: 4010-4017 [Abstract] [Full Text]
Ogata, N., Kouro, T., Yamada, A., Koike, M., Hanai, N., Ishikawa, T., Takatsu, K. (1998). JAK2 and JAK1 Constitutively Associate With an Interleukin-5 (IL-5) Receptor alpha �and beta c Subunit, Respectively, and Are Activated Upon IL-5 Stimulation. Blood 91: 2264-2271 [Abstract] [Full Text]
Coffer, P. J., Schweizer, R. C., Dubois, G. R., Maikoe, T., Lammers, J.-W. J., Koenderman, L. (1998). Analysis of Signal Transduction Pathways in Human Eosinophils Activated by Chemoattractants and the T-Helper 2-Derived Cytokines Interleukin-4 and Interleukin-5. Blood 91: 2547-2557 [Abstract] [Full Text]
Corey, S. J., Dombrosky-Ferlan, P. M., Zuo, S., Krohn, E., Donnenberg, A. D., Zorich, P., Romero, G., Takata, M., Kurosaki, T. (1998). Requirement of Src Kinase Lyn for Induction of DNA Synthesis by Granulocyte Colony-stimulating Factor. J. Biol. Chem. 273: 3230-3235 [Abstract] [Full Text]
Bates, M. E., Busse, W. W., Bertics, P. J. (1998). Interleukin 5�Signals through Shc and Grb2 in Human Eosinophils. Am. J. Respir. Cell Mol. Bio. 18: 75-83 [Abstract] [Full Text]
Yasue, T., Nishizumi, H., Aizawa, S., Yamamoto, T., Miyake, K., Mizoguchi, C., Uehara, S., Kikuchi, Y., Takatsu, K. (1997). A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin�5. Proc. Natl. Acad. Sci. USA 94: 10307-10312 [Abstract] [Full Text]
Pazdrak, K., Adachi, T., Alam, R. (1997). Src Homology 2�Protein Tyrosine Phosphatase (SHPTP2)/Src Homology 2�Phosphatase 2�(SHP2) Tyrosine Phosphatase Is a Positive Regulator of the Interleukin 5�Receptor Signal Transduction Pathways Leading to the Prolongation of Eosinophil Survival. J. Exp. Med. 186: 561-568 [Abstract] [Full Text]
Burton, E. A., Hunter, S., Wu, S. C., Anderson, S. M. (1997). Binding of src-like Kinases to the beta -Subunit of the Interleukin-3 Receptor. J. Biol. Chem. 272: 16189-16195 [Abstract] [Full Text]
Holland, J., Owens, T. (1997). Signaling through Intercellular Adhesion Molecule 1(ICAM-1) in a B Cell Lymphoma Line. THE ACTIVATION OF Lyn TYROSINE KINASE AND THE MITOGEN-ACTIVATED PROTEIN KINASE PATHWAY. J. Biol. Chem. 272: 9108-9112 [Abstract] [Full Text]
de Groot, R. P., van Dijk, T. B., Caldenhoven, E., Coffer, P. J., Raaijmakers, J. A.M., Lammers, J.-W. J., Koenderman, L. (1997). Activation of 12-O-Tetradecanoylphorbol-13-acetate Response Element- and Dyad Symmetry Element-dependent Transcription by Interleukin-5 Is Mediated by Jun N-terminal Kinase/Stress-activated Protein Kinase Kinases. J. Biol. Chem. 272: 2319-2325 [Abstract] [Full Text]
Caldenhoven, E., van Dijk, T., Raaijmakers, J. A. M., Lammers, J.-W. J., Koenderman, L., de Groot, R. P. (1995). Activation of the STAT3/Acute Phase Response Factor Transcription Factor by Interleukin-5. J. Biol. Chem. 270: 25778-25784 [Abstract] [Full Text]
Du, J., Alsayed, Y. M., Xin, F., Ackerman, S. J., Platanias, L. C. (2000). Engagement of the CrkL Adapter in Interleukin-5 Signaling in Eosinophils. J. Biol. Chem. 275: 33167-33175 [Abstract] [Full Text]