Isacke C M, Lindberg R A, Hunter T
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92138.
Mol Cell Biol. 1989 Jan;9(1):232-40. doi: 10.1128/mcb.9.1.232-240.1989.
p36 and p35 are distinct but related proteins that share many structural and biochemical features which were first identified as major substrates for protein-tyrosine kinases. Subsequently, both proteins have been shown to be Ca2+-, phospholipid-, and F-actin-binding proteins that underlie the plasma membrane and are associated with the cortical cytoskeleton. Recent reports have claimed that these proteins function as lipocortins, i.e., phospholipase A2 inhibitors that mediate the anti-inflammatory action of glucocorticoids. To investigate this possibility and to learn more about the functions of p36 and p35, we used human-specific anti-p36 and anti-p35 monoclonal antibodies to determine whether the expression or secretion of either protein was inducible by dexamethasone in the human U-937 myeloid cell line and in other human cell types. Additionally, we examined the levels of mRNA for both proteins. No effect of dexamethasone was observed on p36 or p35 expression at either the mRNA or protein level, nor were these proteins secreted under any of the culture conditions investigated. However, it was observed that in these cells the rate of synthesis and accumulation of both proteins was increased when the U-937 cells were induced to differentiate in culture to adherent macrophagelike cells. This offers a model system with which to study the control of p36 and p35 expression.
p36和p35是不同但相关的蛋白质，它们具有许多结构和生化特征，最初被鉴定为蛋白质酪氨酸激酶的主要底物。随后，这两种蛋白质都被证明是与质膜相关并与皮质细胞骨架相连的钙离子、磷脂和F-肌动蛋白结合蛋白。最近的报道称，这些蛋白质起着脂皮质素的作用，即介导糖皮质激素抗炎作用的磷脂酶A2抑制剂。为了研究这种可能性并更多地了解p36和p35的功能，我们使用了人特异性抗p36和抗p35单克隆抗体来确定地塞米松是否能诱导人U-937髓样细胞系及其他人类细胞类型中这两种蛋白质的表达或分泌。此外，我们检测了这两种蛋白质的mRNA水平。在地塞米松作用下，无论是mRNA水平还是蛋白质水平，均未观察到对p36或p35表达的影响，在所研究的任何培养条件下这两种蛋白质也均未分泌。然而，观察到在这些细胞中，当U-937细胞在培养中被诱导分化为贴壁的巨噬细胞样细胞时，这两种蛋白质的合成和积累速率均增加。这提供了一个用于研究p36和p35表达调控的模型系统。
