Davis Cristina E, Patel Manoj K, Miller James R, John J Edward, Jones Larry R, Tucker Amy L, Mounsey J Paul, Moorman J Randall
Department of Biomedical Engineering, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
Neurochem Res. 2004 Jan;29(1):177-87. doi: 10.1023/b:nere.0000010447.24128.ac.
Phospholemman (PLM) is a 72-amino-acid phosphoprotein that is a major substrate for cAMP-dependent protein kinase, protein kinase C, and NIMA kinase. In lipid bilayers, PLM forms ion channels selective for Cl-, K+, and taurine. Effluxes of these abundant intracellular osmolytes play an important role in the control of dynamic cell volume changes in many cell types. We measured swelling-activated ion currents and regulatory volume decrease (RVD) in human embryonic kidney cells stably overexpressing canine cardiac PLM. In response to swelling, two clonal cell lines overexpressing PLM had increased swelling-activated ion current densities and faster and more extensive RVD. A third clonal cell line overexpressing mutant PLM showed reduced ion current densities and a diminished RVD response. These results suggest a role for PLM in the regulation of cell volume, perhaps as a modulator of an endogenous swelling-activated signal transduction pathway or possibly by participating directly in swelling-induced osmolyte efflux.
磷蛋白（PLM）是一种由72个氨基酸组成的磷蛋白，是环磷酸腺苷依赖性蛋白激酶、蛋白激酶C和NIMA激酶的主要底物。在脂质双分子层中，PLM形成对Cl-、K+和牛磺酸具有选择性的离子通道。这些丰富的细胞内渗透溶质的外流在许多细胞类型中动态细胞体积变化的控制中起着重要作用。我们在稳定过表达犬心脏PLM的人胚肾细胞中测量了肿胀激活的离子电流和调节性容积减小（RVD）。响应肿胀，两个过表达PLM的克隆细胞系具有增加的肿胀激活离子电流密度以及更快、更广泛的RVD。第三个过表达突变型PLM的克隆细胞系显示离子电流密度降低且RVD反应减弱。这些结果表明PLM在细胞体积调节中起作用，可能作为内源性肿胀激活信号转导途径的调节剂，或者可能通过直接参与肿胀诱导的渗透溶质外流。
