A novel regulatory mechanism links PLCγ1 to PDK1
A novel regulatory mechanism links PLCγ1 to PDK1
复制标题
DOI：
10.1242/jcs.100511
复制
发表时间：
2012-07-01
影响因子：
4
通讯作者：
Falasca, Marco
中科院分区：
文献类型：
--
作者：
Raimondi, Claudio;Chikh, Anissa;Falasca, Marco
3-磷酸肌醇依赖性蛋白激酶-1（PDK 1）和磷脂酶C（PLC）γ 1是信号转导中的两个关键酶，其控制若干细胞内过程。尽管事实上，PLC γ 1已经研究了几年，这种酶的激活机制仍然不完全清楚。类似地，虽然PDK 1主要研究其在Akt（调节几种细胞过程的关键酶）活化中的作用，但最近已经变得明显的是，PDK 1在生理和病理条件中的作用不限于Akt活化。在这里，我们表明，PDK 1调节PLC γ 1激活的机制，涉及协会的两种酶和PLC γ 1酪氨酸磷酸化的调制。我们进一步表明，这种新的PDK 1-PLC γ 1通路对于癌细胞侵袭是重要的。PDK 1-PLCc 1通路的鉴定揭示了信号转导中两种最重要的酶之间存在以前未检测到的联系。这可能对我们理解依赖于磷酸肌醇并由PDK 1和PLC γ 1控制的几种细胞功能产生深远的影响。
3-Phosphoinositide-dependent protein kinase-1 (PDK1) and phospholipase C (PLC)gamma 1 are two key enzymes in signal transduction that control several intracellular processes. Despite the fact that PLC gamma 1 has been investigated for several years, the mechanisms of activation of this enzyme are still not completely clear. Similarly, although PDK1 has been mostly investigated for its role in activation of Akt, a crucial enzyme in regulation of several cellular processes, it has become evident recently that the role of PDK1 in physiological and pathological conditions is not limited to Akt activation. Here we demonstrate that PDK1 regulates PLC gamma 1 activation in a mechanism involving association of the two enzymes and modulation of PLC gamma 1 tyrosine phosphorylation. We further show that this novel PDK1-PLC gamma 1 pathway is important for cancer cell invasion. The identification of a PDK1-PLCc1 pathway reveals the existence of a previously undetected link between two of the most important enzymes in signal transduction. This is likely to have profound consequences for our understanding of several cellular functions that are dependent on phosphoinositides and controlled by PDK1 and PLC gamma 1.