Neumann M, Tsapos K, Scheppler J A, Ross J, Franza B R
Freeman Laboratory of Cancer Cell Biology, Cold Spring Harbor Laboratory, New York 11724.
Oncogene. 1992 Nov;7(11):2095-104.
Immune complexes of the product of the c-rel protooncogene and of p105, the p50 NF-kappa B precursor, isolated from human T-lymphoblastoid cell lines are comprised of multiple proteins. Only p105 and human c-Rel (hc-Rel) are common to complexes precipitated with antiserum directed against either p105 or hc-Rel. Both proteins are inducible by phytohemagglutinin (PHA) and phorbol 12-myristate 13-acetate (PMA) and their subcellular distribution is affected by this induction. We demonstrate that the Rel immune complex contains a protein with a molecular weight in the 40 kDa range (p40) which apparently is exclusively cytoplasmic. We were not able to detect p40 in the p105 immune complex, though hc-Rel is present. This indicates that hc-Rel exists in different multi-protein complexes and fits a model of functional regulation mediated by differential protein-protein interaction. We also demonstrate considerable isoform diversity of both hc-Rel and p105. We show that this heterogeneity is, in part, the result of phosphorylation. Furthermore, we demonstrate that p105 and hc-Rel are tyrosine kinase substrates. This finding indicates a role for both proteins in intracellular signal transduction pathways which are modulated by modification of their phosphorylation status.
从人T淋巴母细胞系中分离出的c-rel原癌基因产物与p105（p50 NF-κB前体）的免疫复合物由多种蛋白质组成。用针对p105或人c-Rel（hc-Rel）的抗血清沉淀的复合物中，只有p105和hc-Rel是共同存在的。这两种蛋白质都可被植物血凝素（PHA）和佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）诱导，并且它们的亚细胞分布受这种诱导的影响。我们证明Rel免疫复合物含有一种分子量在40 kDa范围内的蛋白质（p40），它显然只存在于细胞质中。尽管存在hc-Rel，但我们在p105免疫复合物中未能检测到p40。这表明hc-Rel存在于不同的多蛋白复合物中，符合由不同的蛋白质-蛋白质相互作用介导的功能调节模型。我们还证明了hc-Rel和p105都有相当大的异构体多样性。我们表明这种异质性部分是磷酸化的结果。此外，我们证明p105和hc-Rel是酪氨酸激酶底物。这一发现表明这两种蛋白质在细胞内信号转导途径中起作用，这些途径通过其磷酸化状态的改变而受到调节。
