Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, Bahía Blanca, Argentina.
Arch Biochem Biophys. 2010 Feb 1;494(1):7-14. doi: 10.1016/j.abb.2009.11.002. Epub 2009 Nov 10.
In this work, we studied the involvement of PKC and Src in the phosphorylation of ERK1/2, p38 and JNK1 MAPKs and in the modulation of ATF-1, c-Fos, c-Jun and Jun D transcription factors by ATP in MCF-7 breast cancer cells. RT-PCR studies and nucleotide sequence analysis confirmed first the expression of P2Y(2)- and P2Y(4)-receptor subtypes. The use of specific inhibitors and Src antisense oligonucleotides showed that PKC, but not Src, plays a role in the phosphorylation of MAPKs by ATP. ATP stimulated the expression of c-Fos and the phosphorylation c-Jun, Jun D and ATF-1. PKC and Src only participated in c-Fos induction and in ATF-1 phosphorylation. Pharmacological inhibition of MAPKs demonstrated that c-Fos induction and phosphorylation of c-Jun and Jun D, but not of ATF-1, depend on MAPK activation. These results suggest that stimulation of P2Y(2) and P2Y(4) receptors by ATP modulates transcription factors through PKC/MAPKs and PKC/Src pathways in MCF-7 cells.
在这项工作中，我们研究了 PKC 和 Src 在 ERK1/2、p38 和 JNK1 MAPKs 的磷酸化以及 ATP 对 MCF-7 乳腺癌细胞中 ATF-1、c-Fos、c-Jun 和 Jun D 转录因子的调节中的作用。RT-PCR 研究和核苷酸序列分析首先证实了 P2Y(2)-和 P2Y(4)-受体亚型的表达。使用特异性抑制剂和 Src 反义寡核苷酸表明，PKC 而非 Src 在 MAPKs 的磷酸化中起作用。ATP 刺激 c-Fos 的表达和 c-Jun、Jun D 和 ATF-1 的磷酸化。PKC 和 Src 仅参与 c-Fos 的诱导和 ATF-1 的磷酸化。MAPKs 的药理学抑制表明，c-Fos 的诱导和 c-Jun 和 Jun D 的磷酸化，但不是 ATF-1 的磷酸化，依赖于 MAPK 的激活。这些结果表明，ATP 刺激 P2Y(2)和 P2Y(4)受体通过 PKC/MAPKs 和 PKC/Src 途径调节 MCF-7 细胞中的转录因子。
