Abstract

 

Phosphorylation of the signaling component by protein kinase often leads to a kinase cascade or feedback loop. 3-Phosphoinositide-Dependent Kinase 1 (PDK1) signaling pathway diverges into various kinases including Akt and p70 S6 kinase (p70S6k), but a feedback mechanism back to PDK1 remains elusive. Here, we demonstrated that UNC-51-Like Kinase (ULK1), an autophagy initiator kinase downstream of mechanistic Target Of Rapamycin (mTOR), directly phosphorylated PDK1 on Serine 389 at the linker region. Furthermore, our data showed that this phosphorylation might affect the kinase activity of PDK1 toward downstream substrates. These results suggest a possible negative feedback loop between PDK1 and ULK1.