Abstract 1101 Auto-inhibitory Intra-domain Interactions of Phosphoinositide-dependent Kinase-1(PDPK1) are Released by Phosphorylation of the Respective Domains

Human PDPK1 is a master protein kinase that plays a crucial role in cell growth and differentiation by phosphorylating and activating multiple protein kinases, including Akt/PKB, S6K, and SGK. PDPK1 contains an N-terminal region (NTR) spanning 75 amino acids, a central kinase domain (KD), and a C-terminal region (CTR). The CTR contains a pleckstrin homology (PH) domain, which is shown to bind and inhibit the PDPK1-KD. However, the functional role of the NTR in PDPK1 activation remains unclear. In this study, we investigated the roles of both the NTR and CTR of PDPK1 utilizing a yeast strain carrying a temperature-sensitive (ts) allele of the protein kinase Pkh1 (pkh1ts).