Ca2+ signalling mechanisms of the β2 integrin on neutrophils: involvement of phospholipase Cγ2 and Ins(1,4,5)P3
Open accessAbstract
Engagement of β2 integrins triggers a tyrosine kinase-dependent intracellular mobilization and influx of Ca2+ in human neutrophils. However, the transduction pathway involved in generating this Ca2+ signal is obscure. In the present study we identified phospholipase Cγ2 (PLCγ2) as one of the major proteins that was phosphorylated on tyrosine in response to β2 integrin activation. This β2 integrin-induced phosphorylation of PLCγ2 occurred in parallel with an increased accumulation of Ins(1,4,5)P3. The relevance of these observations for the β2 integrin-induced Ca2+ signal was investigated using an inhibitor of PLC signalling pathways, 1-(6-{[17β-3-methoxyoestra-1,3,5(10)-trien-17-yl]amino}hexyl)-1H-pyrrole-2,5-dione (U73122). U73122 dose-dependently (IC50, approx. 0.15 μM) inhibited both the β2 integrin-induced release of Ca2+ from intracellular stores and the subsequent influx of Ca2+ across the plasma membrane. These effects were not observed with the inactive analogue 1-(6-{[17β-3-methoxyoestra-1,3,5(10)-trien-17-yl]amino}hexyl)-pyrrolidine-2,5-dione (U73343). To gain further support for an involvement of PLC-induced Ins(1,4,5)P3 formation in the β2 integrin-induced Ca2+ signal, we searched for the molecular event(s) underlying the effects of U73122. Our experiments revealed that U73122 had no effect on either β2 integrin-induced tyrosine phosphorylation of PLCγ2 (or any of the other proteins) or on the formation of Ins(1,4,5)P3, but it reduced the Ins(1,4,5)P3-induced release of 45Ca2+ from intracellular stores of electropermeabilized cells. Taken together, the present data suggest that the β2 integrin-induced Ca2+ signal in human neutrophils is generated through activation of a PLCγ2-dependent pathway.
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In neutrophils, PLCγ2 mediates intracellular mobilization and influx of Ca2+ upon engagement of β2 integrin.
“In neutrophils, PLCγ2 was implicated in mediating intracellular mobilization and influx of Ca2+ upon engagement of β2 integrin46.”
From PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages (2021) · cites this paper as [46]
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- Kishimoto, T. K. and Anderson, D. C. (1992) in Inflammation : Basic Principles and Clinical Correlates, 2nd edn. (Gallin, J. I., Goldstein, I. M. and Snyderman, R., eds.), pp. 353-406, Raven Press Ltd., New York
- Sanchez-Madrid, F., Nagy, J. A., Robbins, E., Simon, P. and Springer, T. A. (1983) J. Exp. Med. 158, 1785-1803
- Richter, J., Ng-Sikorski, J., Olsson, I. and Andersson, T. (1990) Proc. Natl. Acad. Sci.
- Kanner, S. B., Grosmaire, L. S., Ledbetter, J. A. and Damle, N. K. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7099-7103 Received 9 January 1996/4 March 1996 ; accepted 11 March 1996
- Wright, S.D., Rao, P. E., van Voorhis, W. C., Craigmyle, L. S., Iida, K., Talle, M. A., Westberg, E. F., Goldstein, G. and Silverstein, S. C. (1983) Proc. Natl. Acad. Sci.
- Tatham, P. E. R. and Gomperts, B. D. (1990) in Peptide Hormones : A Practical Approach, vol. 2 (Siddle, K. and Hutton, J. C., eds.), pp. 257-269, IRL Press, Oxford 21
- Snyderman, R. and Uhing, R. J. (1992) in Inflammation : Basic Principles and Clinical Correlates, 2nd edn. (Gallin, J. I., Goldstein, I. M. and Snyderman, R., eds.), pp. 421-439, Raven Press Ltd., New York
- Thastrup, O., Cullen, P. J., Drøbak, B. K., Hanley, M. R. and Dawson, A. P. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 2466-2470
- Kornberg, L. J., Earp, H. S., Turner, C. E., Prockop, C. and Juliano, R. L. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 8392-8396
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- Authors
- HELLBERG, C., MOLONY, L., ZHENG, L., & ANDERSSON, T.
- Affiliations
- Linköping University (SE)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1996-07-15
- Volume
- 317
- Issue
- 2
- Pages
- 403-409
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1217502
- OpenAlex
- W2345689701
- Cited by
- 81
- References
- 0
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 2 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 4
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Svenska Läkaresällskapet
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- neutrophils, calcium signaling, PLCγ2, inositol 1,4,5-trisphosphate, tyrosine phosphorylation, U73122, intracellular calcium release, calcium influx, integrin activation, signal transduction
- MeSH terms
- Calcium, Estrenes, Humans, Isoenzymes, Neutrophils, Phosphodiesterase Inhibitors, Type C Phospholipases, Protein-Tyrosine Kinases, Pyrrolidinones, Signal Transduction, Inositol 1,4,5-Trisphosphate, CD18 Antigens, Phospholipase C gamma
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