Shiroo M, Matsushima K
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21701.
Cytokine. 1990 Jan;2(1):13-20. doi: 10.1016/1043-4666(90)90038-u.
Tumor necrosis factor (TNF) and interleukin-1 (IL-1) enhanced the phosphorylation of identical cytosolic 65 kDa protein (P65 or l-plastin) and 74 kDa protein (P74) at serine residues in human peripheral blood mononuclear cells (PBMC). The isoelectric points of P65 and P74 were 5.6 and 4.7 to 5.0, respectively. The phosphorylation of these proteins increased with a few minutes and reached maximal levels of approximately 3 times the unstimulated levels by 10 minutes. The phosphorylation of P65 and P74 was extensively enhanced by a potent protein kinase C (PKC) activator, PMA. However, there was no translocation of PKC from cytosol to membrane in PBMC that was stimulated with either TNF or IL-1, which suggests that PKC does not participate in TNF or IL-1 signal transduction. cAMP dependent protein (PKA) activators, forskolin and PGE2, failed to increase the phosphorylation, which is in agreement with the data showing that neither TNF nor IL-1 increased cAMP levels in PBMC. These results suggest that induction of phosphorylation of P65 and P74 by TNF and IL-1 is not mediated by PKC and PKA but may be mediated by another protein kinase and result in overlapping of biological activities between TNF and IL-1.
肿瘤坏死因子（TNF）和白细胞介素-1（IL-1）可增强人外周血单个核细胞（PBMC）中相同的65 kDa胞质蛋白（P65或l-丝束蛋白）和74 kDa蛋白（P74）丝氨酸残基的磷酸化。P65和P74的等电点分别为5.6和4.7至5.0。这些蛋白质的磷酸化在几分钟内增加，到10分钟时达到约为未刺激水平3倍的最大水平。强效蛋白激酶C（PKC）激活剂PMA可广泛增强P65和P74的磷酸化。然而，在用TNF或IL-1刺激的PBMC中，PKC没有从胞质溶胶转位到细胞膜，这表明PKC不参与TNF或IL-1信号转导。cAMP依赖性蛋白（PKA）激活剂福斯高林和前列腺素E2未能增加磷酸化，这与TNF和IL-1均未增加PBMC中cAMP水平的数据一致。这些结果表明，TNF和IL-1诱导的P65和P74磷酸化不是由PKC和PKA介导的，而是可能由另一种蛋白激酶介导，并导致TNF和IL-1之间的生物学活性重叠。
