Inhibitors of Farnesyl and Geranylgeranyl Methyltransferases Prevent β2Integrin-Induced Actin Polymerization without Affecting β2Integrin-Induced Ca2+Signaling in Neutrophils

Inhibitors of Farnesyl and Geranylgeranyl Methyltransferases Prevent β2Integrin-Induced Actin Polymerization without Affecting β2Integrin-Induced Ca2+Signaling in Neutrophils

The role of prenylated proteins such as low molecular weight G-proteins (LMW G-proteins) in β2integrin-dependent neutrophil signal transduction was investigated using two methyltransferase inhibitors, N-Acetyl-S-farnesyl-L-cysteine (AFC) and N-Acetyl-S-geranylgeranyl-L-cysteine (AGGC), and an inacti...

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Veröffentlicht in:Biochemical and biophysical research communications 1996-06, Vol.223 (3), p.612-617
Hauptverfasser: Molony, Leslie, Ng-Sikorski, Janet, Hellberg, Carina, Andersson, Tommy
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Sprache:eng
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container_issue 3
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container_title Biochemical and biophysical research communications
container_volume 223
creator Molony, Leslie
Ng-Sikorski, Janet
Hellberg, Carina
Andersson, Tommy
description The role of prenylated proteins such as low molecular weight G-proteins (LMW G-proteins) in β2integrin-dependent neutrophil signal transduction was investigated using two methyltransferase inhibitors, N-Acetyl-S-farnesyl-L-cysteine (AFC) and N-Acetyl-S-geranylgeranyl-L-cysteine (AGGC), and an inactive control, N-acetyl-S-geranyl-L-cysteine (AGC). The drugs did not affect β2integrin-induced protein tyrosine phosphorylations or cytosolic calcium transients. However, AGGC inhibited β2integrin-induced actin polymerization (IC50of ∼45nM), as did AFC (IC50of ∼5.5 μM), but not AGC. Thus, prenylated proteins, such as LMW G-proteins, are responsible for β2integrin regulation of actin filament reorganization downstream of tyrosine kinase(s) activation, and represent a β2integrin signaling mechanism distinct from the pathway which regulates cytosolic calcium transients.
doi_str_mv 10.1006/bbrc.1996.0943
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title Inhibitors of Farnesyl and Geranylgeranyl Methyltransferases Prevent β2Integrin-Induced Actin Polymerization without Affecting β2Integrin-Induced Ca2+Signaling in Neutrophils
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