Niggli V, Keller H
Department of Pathology, University of Bern, Switzerland.
J Biol Chem. 1991 Apr 25;266(12):7927-32.
We have investigated the effect of staurosporine-type protein kinase inhibitors, displaying different enzyme specificity, on the association of actin with the neutrophil cytoskeleton. In resting cells, nanomolar concentrations of staurosporine induced a rapid increase in cytoskeleton-associated actin. Other inhibitors, more specific for protein kinase C (PKC) or kinases dependent on cyclic nucleotides, induced a much smaller response, indicating that inhibition of these enzymes is not involved in the staurosporine-dependent rise. Therefore, inhibition of an unknown staurosporine-sensitive enzyme, not identical with PKC or one of the cyclic nucleotide-dependent kinases, can trigger an increase in cytoskeletal actin. It is well known that chemotactic peptide induces a rapid rise in cytoskeletal actin, followed by a decrease at later times after the onset of activation. Preincubation with CGP 41,251, a relatively specific inhibitor for PKC, did not affect these two events at concentrations of the drug which, in separate experiments, inhibited markedly phorbol ester induced protein phosphorylation in intact neutrophils. Thus the chemotactic peptide-induced changes in the level of cytoskeletal actin appear to be independent of PKC activation.
我们研究了显示出不同酶特异性的星形孢菌素型蛋白激酶抑制剂对肌动蛋白与中性粒细胞细胞骨架结合的影响。在静息细胞中，纳摩尔浓度的星形孢菌素可导致细胞骨架相关肌动蛋白迅速增加。其他对蛋白激酶C（PKC）或依赖环核苷酸的激酶更具特异性的抑制剂诱导的反应要小得多，这表明这些酶的抑制与星形孢菌素依赖性增加无关。因此，抑制一种未知的对星形孢菌素敏感的酶（不同于PKC或环核苷酸依赖性激酶之一）可引发细胞骨架肌动蛋白增加。众所周知，趋化肽会导致细胞骨架肌动蛋白迅速增加，随后在激活开始后的较晚时间减少。用CGP 41,251（一种相对特异性的PKC抑制剂）预孵育，在该药物浓度下，这两个事件均未受到影响，而在单独的实验中，该浓度的药物可显著抑制佛波酯诱导的完整中性粒细胞中的蛋白磷酸化。因此，趋化肽诱导的细胞骨架肌动蛋白水平变化似乎与PKC激活无关。
