Apgar J R
Scripps Research Institute, La Jolla, California 92037.
Mol Biol Cell. 1994 Mar;5(3):313-22. doi: 10.1091/mbc.5.3.313.
Crosslinking of the IgE receptor on rat basophilic leukemia (RBL) cells using the multivalent antigen DNP-BSA leads to a rapid and sustained increase in the filamentous actin content of the cells. Stimulation of RBL cells through the adenosine receptor also induces a very rapid polymerization of actin, which peaks in 45-60 s and is equivalent in magnitude to the F-actin response elicited through stimulation of the IgE receptor. However, in contrast to the IgE mediated response, which remains elevated for over 30 min, the F-actin increase induced by the adenosine analogue 5'-(N-ethylcarboxamido)-adenosine (NECA) is relatively transient and returns to baseline values within 5-10 min. While previous work has shown that the polymerization of actin in RBL cells stimulated through the IgE receptor is mediated by protein kinase C (PKC), protein kinase inhibitors have no effect on the F-actin response activated through the adenosine receptor. In contrast, pretreatment of the cells with pertussis toxin completely inhibits the F-actin response to NECA but has relatively little effect on the response induced through the IgE receptor. Stimulation of RBL cells through either receptor causes increased production of phosphatidylinositol mono-phosphate (PIP) and phosphatidylinositol bis-phosphate (PIP2), which correlates with the F-actin response. Production of PIP and PIP2 may be important downstream signals since these polyphosphoinositides are able to regulate the interaction of gelsolin and profilin with actin. Thus the polymerization of actin can be triggered through either the adenosine receptor or the IgE receptor, but different upstream signaling pathways are being used. The IgE mediated response requires the activation of PKC while stimulation through the adenosine receptor is PKC independent but involves a G protein.
使用多价抗原二硝基苯基牛血清白蛋白(DNP-BSA)交联大鼠嗜碱性白血病(RBL)细胞上的IgE受体,会导致细胞丝状肌动蛋白含量迅速且持续增加。通过腺苷受体刺激RBL细胞也会诱导肌动蛋白非常快速地聚合,在45 - 60秒达到峰值,其幅度与通过刺激IgE受体引发的F-肌动蛋白反应相当。然而,与持续升高超过30分钟的IgE介导的反应不同,腺苷类似物5'-(N-乙基羧酰胺基)-腺苷(NECA)诱导的F-肌动蛋白增加相对短暂,并在5 - 10分钟内恢复到基线值。虽然先前的研究表明,通过IgE受体刺激的RBL细胞中肌动蛋白的聚合是由蛋白激酶C(PKC)介导的,但蛋白激酶抑制剂对通过腺苷受体激活的F-肌动蛋白反应没有影响。相反,用百日咳毒素预处理细胞会完全抑制对NECA的F-肌动蛋白反应,但对通过IgE受体诱导的反应影响相对较小。通过任一受体刺激RBL细胞都会导致磷脂酰肌醇单磷酸(PIP)和磷脂酰肌醇二磷酸(PIP2)的产生增加,这与F-肌动蛋白反应相关。PIP和PIP2的产生可能是重要的下游信号,因为这些多磷酸肌醇能够调节凝溶胶蛋白和前纤维蛋白与肌动蛋白的相互作用。因此,肌动蛋白的聚合可以通过腺苷受体或IgE受体触发,但使用的是不同的上游信号通路。IgE介导的反应需要PKC的激活,而通过腺苷受体的刺激不依赖PKC,但涉及一种G蛋白。