Skip to main content
SpringerLink
Log in

Interleukin-8 activates microtubule-associated protein 2 kinase (ERK1) in human neutrophils

  • Protein Phosphorylation in Signal Transduction
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The signal transduction initiated by the human cytokine interleukin-8 (IL-8), the main chemotactic cytokine for neutrophils, was investigated and found to encompass the stimulation of protein kinases. More specifically, IL-8 caused a transient, dose and time dependent activation of a Ser/Thr kinase activity towards myelin basic protein (MBP) and the MBP-derived peptide APRTPGGRR patterned after the specific concensus sequence in MBP for ERK enzymes. The activated MBP kinase was furthermore identified as an extracellular signal regulated kinase (ERK1) based on several criteria such as substrate specificity, molecular weight, activation-dependent mobility shift, and recognition by anti-ERK antibodies. For comparison, the chemotactic response of neutrophils to a stimulus of bacterial origin (fMet-Leu-Phe or fMLP) was also examined and found to involve the activation of a similar ERK enzyme. The present data clearly indicate that in terminally differentiated, non-proliferating human cells, the MBP kinase/ERK activity can serve other purposes than mitogenic signaling, and that processes such as chemotaxis, induced by bacterial peptides as well as by human cytokines like IL-8, involve the regulation of ERK enzyme.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Chapter © 2014

Chapter © 2017

Abbreviations

IL-8:

interleukin-8

fMLP:

fMet-Leu-Phe

MBP:

myelin basic protein

ERK:

extracellular signal regulated kinase

MAP2:

microtubule-associated protein 2

PK-A:

cAMP dependent protein kinase

PKI:

protein kinase inhibitor

PMSF:

phenyl-methanesulfonyl fluoride

PVDF:

poly-vinylidene difluoride

HBSF:

Hank's buffered salt solution

DAB:

3,3′-diaminobenzidine tetrahydrochloride

PNPP:

p-nitrophenyl-phosphate

HSA:

human serum albumin

EGTA:

[ethylenebis (oxyethylenenitrilo)]tetraacetic acid

SDS-PAGE:

sodium dodecyl sulfate polyacrylamide gel electrophoresis

References

  1. Van Damme J: Interleukin-8 and related molecules. In: AW Thompson (ed.) The Cytokine Handbook. Academic Press, London, 1991, pp 201–214

    Google Scholar 

  2. Haslett C, Savil JS, Meagher L: The neutrophil. Curr Opin Immunol 2: 10–18, 1989

    PubMed  Google Scholar 

  3. Hugli TE: Chemotaxis. Curr Opin Immunol 2: 19–27, 1989

    PubMed  Google Scholar 

  4. Van Damme J, Van Beeumen J, Opdenakker G, Billiau A: A novel, NH2-terminal sequence-characterized human monokine possessing neutrophil-chemotactic, skin reactive, and granulocytosis-promoting activity. J Exp Med 167: 1364–1476, 1988

    PubMed  Google Scholar 

  5. Oppenheim JJ, Zachariae COC, Mukaida N, Matushima K: Properties of the novel proinflammatory supergene ‘intercrine’ cytokine family. Annu Rev Immunol 9: 617–648, 1991

    PubMed  Google Scholar 

  6. Holmes WE, Lee J, Kuang W-J, Rice GC, Wood W: Structure and functional expression of a human interleukin-8 receptor. Science 253: 1278–1280, 1991

    PubMed  Google Scholar 

  7. Murphy PM, Tiffany HL: Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science 253: 1280–1283, 1991

    PubMed  Google Scholar 

  8. Kupper RW, Dewald B, Jakobs KH, Baggiolini M, Gierschik P: G-protein activation by interleukin 8 and related cytokines in human neutrophil plasma membranes. Biochem J 282: 429–434, 1992

    PubMed  Google Scholar 

  9. Pevery P, Walz A, Dewald B, Baggiolini M: A novel neutrophil-activating factor produced by human mononeuclear phagocytes. J Exp Med 167: 1547–1559, 1988

    PubMed  Google Scholar 

  10. Boulton TG, Nye SH, Robbins DJ, Ip NJ, Radziejewska E, Morgenbesser SD, DePinho RA, Panayotatos N, Cobb M, Yancopoulos GD: ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell 65: 663–675, 1991

    PubMed  Google Scholar 

  11. Van Damme J, Van Beeumen J, Conings R, Decock B, Billiau A: Purification of granulocyte chemotactic peptide/interleukin-8 reveals N-terminal sequence heterogeneity similar to that of β-thromboglobulin. Eur J Biochem 181: 337–344, 1989

    PubMed  Google Scholar 

  12. Gotoh Y, Nishida E, Yamashita T, Hoshi M, Kawakami M, Sakai H: Microtubule-associated-protein (MAP) kinase activated by nerve growth factor and epidermal growth factor in PC12 cells. Identity with the mitogen-activated MAP kinase of fibroblastic cells. Eur J Biochem 193: 661–669, 1990

    PubMed  Google Scholar 

  13. Campos-Gonzalez R, Glenney JR: Temperature-dependent tyrosine phosphorylation of microtubule-associated protein kinase in epidermal growth factor-stimulated human fibroblasts. Cell Regul 2: 663–673, 1991

    PubMed  Google Scholar 

  14. Thelen M, Peveri P, Kernen P, Von Tscharner V, Walz A, Baggiolini M: Mechanism of neutrophil activation by NAF, a novel monocyte-derived peptide agonist. FASEB J 2: 2702–2706, 1988

    PubMed  Google Scholar 

  15. De Vries AMM, Burgering BMTh, Leevers SJ, Marshall CJ, Bos JL: Involvement of p21ras in activation of extracellular signal-regulated kinase 2. Nature 357: 602–604, 1992

    PubMed  Google Scholar 

  16. Rampart M, Herman AG, Grillet B, Opdenakker G, Van Damme J: Development and application of a radioimmunoassay for interleukin-8 in synovial fluids from patients with inflammatory Joint disease. Laboratory Investigation 66: 512–518, 1992

    PubMed  Google Scholar 

  17. Lord R: Assessment of neutrophil function: an introduction. Med Lab Sci 46: 347–356, 1989

    PubMed  Google Scholar 

  18. Haynes AP, Fletcher J: Neutrophil function tests. Baillière's Clinical Haematology 3: 871–887, 1990

    Google Scholar 

  19. Anderson NG, Maller JL, Tonks NK, Sturgill TW: Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. Nature 343: 651–653, 1990

    PubMed  Google Scholar 

  20. Gotoh Y, Nishida E, Matsuda S, Shiina N, Kosako K, Shiokawa K, Akiyama T, Ohta K, Sakai H:In vitro effects on microtubule dynamics of purified Xenopus M phase-activated MAP kinase. Nature 349: 251–254, 1991

    PubMed  Google Scholar 

  21. Goldstein IM, Hoffstein S, Gallin J, Weissmann G: Mechanism of lysosomal enzyme release from human leukocytes: microtubule assembly and membrane fusion induced by a component of complement. Proc Natl Acad Sci USA 70: 2916–2920, 1973

    PubMed  Google Scholar 

  22. Grinstein S, Furuya W: Chemoattractant-induced tyrosine phosphorylation and activation of microtubule-associated protein kinase in human neutrophils. J Biol Chem 267: 18122–18125, 1992

    PubMed  Google Scholar 

  23. Samanta AK, Oppenheim JJ, Matsushima K: Interleukin 8 (monocyte-derived neutrophil chemotactic factor) dynamically regulates its own receptor expression on human neutrophils. J Biol Chem 265: 183–189, 1990

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit te Leuven, Campus Gasthuisberg, B-3171, Belgium

    Johan Van Lint, Jo Van Damme, Alfons Billiau, Wilfried Merlevede & Jackie R. Vandenheede

  2. Rega Institute for Medical Research, Katholieke Universiteit te Leuven, Campus Gasthuisberg, B-3171, Belgium

    Jo Van Damme & Alfons Billiau

Authors
  1. Johan Van Lint
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jo Van Damme
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alfons Billiau
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wilfried Merlevede
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jackie R. Vandenheede
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Van Lint, J., Van Damme, J., Billiau, A. et al. Interleukin-8 activates microtubule-associated protein 2 kinase (ERK1) in human neutrophils. Mol Cell Biochem 127, 171–177 (1993). https://doi.org/10.1007/BF01076768

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01076768

Key words

Search

Navigation