PMA‐induced activation of the p42/44ERK‐ and p38RK‐MAP kinase cascades in HL‐60 cells is PKC dependent but not essential for differentiation to the macrophage‐like phenotype
PMA‐induced activation of the p42/44ERK‐ and p38RK‐MAP kinase cascades in HL‐60 cells is PKC dependent but not essential for differentiation to the macrophage‐like phenotype
复制标题
PMA 诱导的 HL-60 细胞中 p42/44ERK- 和 p38RK-MAP 激酶级联的激活是 PKC 依赖性的，但对于分化为巨噬细胞样表型不是必需的
DOI：
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发表时间：
1997
影响因子：
5.6
通讯作者：
M. Gaestel
中科院分区：
文献类型：
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作者：
Heidi Schultz;K. Engel;M. Gaestel
采用不同的蛋白激酶抑制剂研究了肉豆蔻酸磷酯（PMA）诱导HL - 60细胞向巨噬细胞样表型分化的信号机制。蛋白激酶C抑制剂Ro 31‐8220特异性阻断PMA诱导的HL‐60细胞分化、p42/44ERK‐和p38RK‐MAP激酶级联的激活和Hsp27‐磷酸化。由于Ro 31‐8220不抑制mapk激酶级联反应的激活，如表皮生长因子（EGF）、热休克或大霉素等与PKC无关的信号，因此只有PMA‐诱导的mapk激酶激活可能发生在PKC的下游。MEK1抑制剂PD 098059和p38RK抑制剂SB 203580也被用来分析PMA诱导的PKC依赖性MAP激酶激活是否参与分化过程。在一定条件下，PD 098059可以完全阻断PMA诱导的p42ERK的激活，通过使用底物髓鞘碱性蛋白的免疫沉淀激酶检测。通过MAPKAP激酶2对底物Hsp27的活性判断，SB 203580特异性抑制p38RK的活化，并阻断Hsp27在细胞中的磷酸化。相比之下，PD 098059和SB 203580以及两种抑制剂都不能共同阻止PMA诱导的HL - 60细胞向巨噬细胞样表型的分化。结果表明，在PKC下游的HL - 60细胞中存在PMA诱导的信号分化，导致非分化所必需的MAP激酶的激活，以及其他迄今尚未确定的负责分化的靶标的磷酸化。j .细胞。生理学报，33(3):391 - 398。©1997 Wiley‐Liss, Inc。
The signaling mechanisms leading to phorbol ester myristate (PMA)‐induced differentiation of HL‐60 cells to the macrophagelike phenotype were investigated by using different protein kinase inhibitors. The protein kinase C inhibitor Ro 31‐8220 specifically blocks PMA‐induced differentiation, activation of the p42/44ERK‐ and p38RK‐MAP kinase cascades and Hsp27‐phosphorylation in HL‐60 cells. Because Ro 31‐8220 does not inhibit activation of the MAP kinase cascades by protein kinase C (PKC)‐independent signals such as epidermal growth factor (EGF), heat shock, or anisomycin in these cells, only PMA‐induced activation of the MAP kinases can be downstream of PKC. The MEK1 inhibitor PD 098059 and the p38RK inhibitor SB 203580 also were used to analyze whether the PMA‐induced PKC‐dependent activation of MAP kinases is involved in the differentiation process. Under certain conditions, PD 098059 can completely block the PMA‐induced activation of the p42ERK as monitored by imunoprecipitation kinase assay by using the substrate myelin basic protein. SB 203580 specifically inhibits activation of p38RK as judged by MAPKAP kinase 2 activity against the substrate Hsp27 and also blocks Hsp27 phosphorylation in the cells. In contrast, neither PD 098059 nor SB 203580 nor both inhibitors together prevent PMA‐induced differentiation of the HL‐60 cells to the macrophagelike phenotype. The results suggest the existence of a diversification of PMA‐induced signaling in HL‐60 cells downstream of PKC, leading to activation of MAP kinases that are not essential for differentiation and to phosphorylation of other, so far unidentified, targets responsible for differentiation. J. Cell. Physiol. 173:310–318, 1997. © 1997 Wiley‐Liss, Inc.
人骨髓性白血病细胞单核细胞分化过程中 Raf-1 和丝裂原激活蛋白激酶的激活。
DOI：
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发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kharbanda,S;Saleem,A;Emoto,Y;Stone,R;Rapp,U;Kufe,D
通讯作者：
Kufe,D