Phosphorylated HSP27 modulates the association of phosphorylated caldesmon with tropomyosin in colonic smooth muscle.
Phosphorylated HSP27 modulates the association of phosphorylated caldesmon with tropomyosin in colonic smooth muscle.
复制标题
磷酸化 HSP27 调节结肠平滑肌中磷酸化钙结合蛋白与原肌球蛋白的关联。
DOI：
10.1152/ajpgi.00350.2005
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Bitar,KhalilN
中科院分区：
文献类型：
--
作者：
Somara,Sita;Bitar,KhalilN
细丝对平滑肌收缩的调节包括对激动剂刺激反应的收缩蛋白的磷酸化、结合和解离。钙调蛋白的磷酸化减弱了它与肌动蛋白的结合，导致肌动球蛋白的相互作用和收缩。目前来自结肠平滑肌细胞的数据表明，乙酰胆碱诱导了钙调蛋白与蛋白激酶Cα的显著关联，并持续地将789位的钙调蛋白磷酸化。此外，乙酰胆碱诱导磷酸钙调蛋白与热休克蛋白(HSP)27的结合显著和持续增加，同时也增加了磷酸钙调蛋白与原肌球蛋白的解离。在细丝水平上，HSP27在乙酰胆碱诱导的收缩蛋白结合中起着至关重要的作用。目前，用非磷酸化的HSP27突变的c DNA转染的结肠平滑肌细胞的数据表明，磷酸化的HSP27的缺失抑制了乙酰胆碱诱导的钙调蛋白的磷酸化。我们的结果进一步表明，磷酸化HSP27的存在显著增强了乙酰胆碱诱导的磷酸化钙结合蛋白与HSP27的持续结合，同时增加了乙酰胆碱诱导的磷酸化钙结合蛋白与原肌球蛋白的解离。因此，我们提出了一个模型，即在乙酰胆碱诱导钙调蛋白(Ser789)磷酸化后，磷酸化的钙调蛋白(Ser789)与磷酸化的热休克蛋白27的结合导致重要的构象变化，导致磷酸化的钙调蛋白与原肌球蛋白的解离。这导致原肌球蛋白在肌动蛋白上的滑动，从而暴露了肌球蛋白与肌动蛋白相互作用的肌球蛋白结合部位。
Thin-filament regulation of smooth muscle contraction involves phosphorylation, association, and dissociation of contractile proteins in response to agonist stimulation. Phosphorylation of caldesmon weakens its association with actin leading to actomyosin interaction and contraction. Present data from colonic smooth muscle cells indicate that acetylcholine induced a significant association of caldesmon with PKCα and sustained phosphorylation of caldesmon at ser789. Furthermore, acetylcholine induced significant and sustained increase in the association of phospho-caldesmon with heat-shock protein (HSP)27 with concomitant increase in the dissociation of phospho-caldesmon from tropomyosin. At the thin filament level, HSP27 plays a crucial role in acetylcholine-induced association of contractile proteins. Present data from colonic smooth muscle cells transfected with non-phospho-HSP27 mutant cDNA indicate that the absence of phospho-HSP27 inhibits acetylcholine-induced caldesmon phosphorylation. Our results further indicate that the presence of phospho-HSP27 significantly enhances acetylcholine-induced sustained association of phospho-caldesmon with HSP27 with a concomitant increase in acetylcholine-induced dissociation of phospho-caldesmon from tropomyosin. We thus propose a model whereby upon acetylcholine-induced phosphorylation of caldesmon at ser789, the association of phospho-caldesmon (ser789) with phospho-HSP27 results in an essential conformational change leading to dissociation of phospho-caldesmon from tropomyosin. This leads to the sliding of tropomyosin on actin thus exposing the myosin binding sites on actin for actomyosin interaction.