Synthesis of p36 and p35 is increased when U-937 cells differentiate in culture but expression is not inducible by glucocorticoids.

Synthesis of p36 and p35 is increased when U-937 cells differentiate in culture but expression is not inducible by glucocorticoids.
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DOI:
10.1128/mcb.9.1.232
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发表时间:
1989
影响因子:
5.3
通讯作者:
C. Isacke;R. Lindberg;T. Hunter
C. Isacke;R. Lindberg;T. Hunter
中科院分区:
生物学2区
文献类型:
--
作者:
C. Isacke;R. Lindberg;T. Hunter

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P36和P35是截然不同但又相关的蛋白质,它们有许多共同的结构和生化特征,最初被确定为蛋白质酪氨酸激酶的主要底物。随后,这两种蛋白都被证明是钙离子、磷脂和F-肌动蛋白结合的蛋白,它们位于质膜之下,与皮质细胞骨架相关。最近的报道称,这些蛋白的功能是脂皮质素,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,我们使用了人特有的抗p36和抗p35的单抗来确定地塞米松是否可以在人U-937髓系细胞系和其他类型的人细胞中诱导表达或分泌这两种蛋白。此外,我们还检测了这两种蛋白质的mRNA水平。地塞米松对p36或p35蛋白的表达没有影响,在所研究的培养条件下也没有这些蛋白的分泌。然而,观察到当U-937细胞在培养中被诱导分化为贴壁巨噬细胞时,这两种蛋白质的合成和积累速度都有所增加。这为研究p36和p35的表达调控提供了一个模型系统。
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.