Edes I, Kranias E G
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267-0575.
Membr Biochem. 1987;7(3):175-92. doi: 10.3109/09687688709039993.
Calcium fluxes across the sarcoplasmic reticulum membrane are regulated by phosphorylation of a 27,000-dalton membrane-bound protein termed phospholamban. Phospholamban is phosphorylated by three different protein kinases (cAMP-dependent, Ca2+.CAM-dependent and Ca2+.phospholipid dependent) at apparently distinct sites. Phosphorylation by each of the protein kinases increases the rates of active calcium transport by sarcoplasmic reticulum vesicles. The stimulatory effects of protein kinases on the calcium pump may be reversed by an endogenous protein phosphatase activity. The phosphoprotein phosphatase can dephosphorylate both the cAMP-dependent and the Ca2+.CAM-dependent sites of phospholamban. Phosphorylation of phospholamban also occurs in situ, in perfused beating hearts, during the peak of the inotropic response to beta-adrenergic stimulation. Reversal of the stimulatory effects is associated with dephosphorylation of phospholamban. Thus, in vivo and in vitro studies suggest that phospholamban is a regulator for the calcium pump in cardiac sarcoplasmic reticulum. The degree of phospholamban phosphorylation determined by the interaction of specific protein kinases and phosphatases may represent an important control for sarcoplasmic reticulum function and, thus, for the contraction-relaxation cycle in the myocardium. In this review, we summarize recent evidence on physical and structural properties of phospholamban, the proposed structural molecular models for this protein, and the significance of its regulatory role both in vitro and in situ.
跨肌浆网（肌质网）膜的钙通量受一种称为受磷蛋白的27000道尔顿膜结合蛋白磷酸化的调节。受磷蛋白可被三种不同的蛋白激酶（环磷酸腺苷依赖性、钙离子-钙调蛋白依赖性和钙离子-磷脂依赖性）在明显不同的位点磷酸化。每种蛋白激酶的磷酸化作用都会增加肌浆网小泡主动钙转运的速率。蛋白激酶对钙泵的刺激作用可能会被一种内源性蛋白磷酸酶活性逆转。该磷蛋白磷酸酶可使受磷蛋白的环磷酸腺苷依赖性位点和钙离子-钙调蛋白依赖性位点去磷酸化。在对β-肾上腺素能刺激的变力反应高峰期，受磷蛋白的磷酸化也会在灌注的跳动心脏中发生于原位。刺激作用的逆转与受磷蛋白的去磷酸化有关。因此，体内和体外研究表明，受磷蛋白是心肌肌浆网中钙泵的一种调节因子。由特定蛋白激酶和磷酸酶相互作用所决定的受磷蛋白磷酸化程度可能是对肌浆网功能以及心肌收缩-舒张周期的一种重要调控。在这篇综述中，我们总结了关于受磷蛋白物理和结构特性的最新证据、该蛋白的拟议结构分子模型以及其在体外和原位调节作用的重要性。
