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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July 1996
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Research Article|
July 15 1996
Ca2+ signalling mechanisms of the β2 integrin on neutrophils: involvement of phospholipase Cγ2 and Ins(1,4,5)P3
Carina HELLBERG;
Carina HELLBERG
*
1Department of Cell Biology, Linköping University, S-58185 Linköping, Sweden
*To whom correspondence should be addressed.
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Leslie MOLONY;
Leslie MOLONY
†
1Department of Cell Biology, Linköping University, S-58185 Linköping, Sweden
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Limin ZHENG;
Limin ZHENG
1Department of Cell Biology, Linköping University, S-58185 Linköping, Sweden
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Tommy ANDERSSON
Tommy ANDERSSON
1Department of Cell Biology, Linköping University, S-58185 Linköping, Sweden
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Biochem J (1996) 317 (2): 403–409.
Article history
Received:
January 09 1996
Revision Received:
March 04 1996
Accepted:
March 11 1996
Citation
Carina HELLBERG, Leslie MOLONY, Limin ZHENG, Tommy ANDERSSON; Ca2+ signalling mechanisms of the β2 integrin on neutrophils: involvement of phospholipase Cγ2 and Ins(1,4,5)P3. Biochem J 15 July 1996; 317 (2): 403–409. doi: https://doi.org/10.1042/bj3170403
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