Centre for Diabetes, Blizard Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK.
J Cell Sci. 2012 Jul 1;125(Pt 13):3153-63. doi: 10.1242/jcs.100511. Epub 2012 Mar 27.
3-Phosphoinositide-dependent protein kinase-1 (PDK1) and phospholipase C (PLC)γ1 are two key enzymes in signal transduction that control several intracellular processes. Despite the fact that PLCγ1 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 PLCγ1 activation in a mechanism involving association of the two enzymes and modulation of PLCγ1 tyrosine phosphorylation. We further show that this novel PDK1-PLCγ1 pathway is important for cancer cell invasion. The identification of a PDK1-PLCγ1 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 PLCγ1.
3-磷酸肌醇依赖的蛋白激酶-1（PDK1）和磷脂酶 C（PLC）γ1 是信号转导中的两种关键酶，它们控制着几种细胞内过程。尽管 PLCγ1 已经研究了多年，但该酶的激活机制仍不完全清楚。同样，尽管 PDK1 主要因其在 Akt 激活中的作用而被研究，Akt 是调节几种细胞过程的关键酶，但最近已经明显表明，PDK1 在生理和病理条件下的作用不仅限于 Akt 激活。在这里，我们证明 PDK1 通过涉及两种酶的关联和 PLCγ1 酪氨酸磷酸化的调节来调节 PLCγ1 的激活。我们进一步表明，这种新的 PDK1-PLCγ1 途径对于癌细胞的侵袭很重要。PDK1-PLCγ1 途径的鉴定揭示了信号转导中最重要的两种酶之间以前未检测到的联系。这很可能对我们理解依赖于磷酸肌醇并受 PDK1 和 PLCγ1 控制的几种细胞功能产生深远影响。
