New lessons from an old master

3-phosphoinositide-dependent kinase 1 (PDK1) is an essential protein kinase that regulates signaling pathways involved in growth, survival, and proliferation. Often dubbed a ‘master kinase’, it controls the activity of up to 23 other downstream kinases. However, whether its own activity is regulated is controversial. The lab of Thomas Leonard has now elucidated the mechanism of activation of PDK1. Their findings, published in Nature Communications, show that signaling lipids relieve autoinhibition of PDK1, which permits its dimerization and activation on the membrane.