A novel regulatory mechanism links PLC gamma 1 to PDK1

作者：Raimondi Claudio; Chikh Anissa; Wheeler Ann P; Maffucci Tania; Falasca Marco^*

来源：Journal of Cell Science, 2012, 125(13): 3153-3163.

DOI：10.1242/jcs.100511

• Cell invasion
• Cell signalling
• 3-Phosphoinositide-dependent protein kinase-1
• Phosphoinositide 3-kinase
• Phospholipase C gamma 1

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.

• 出版日期2012-7-1