Protein Kinase C Isotypes Controlled by Phosphoinositide 3-Kinase Through the Protein Kinase PDK1

TLDR

Conserved phosphorylation sites in the PKA, PKG, and PKC subfamilies suggest that PDK1 may phosphorylate PKC isotypes. PDK1 phosphorylates the activation loop of PKCζ and PKCδ in vitro and in a PI3K‑dependent manner in vivo, and all tested PKC family members form complexes with PDK1, while PDK1‑dependent phosphorylation of PKCδ is stimulated by PKC and PDK1 activators and by serum in a PI3K‑dependent manner, enhanced by PDK1 coexpression.

Abstract

Phosphorylation sites in members of the protein kinase A (PKA), PKG, and PKC kinase subfamily are conserved. Thus, the PKB kinase PDK1 may be responsible for the phosphorylation of PKC isotypes. PDK1 phosphorylated the activation loop sites of PKCζ and PKCδ in vitro and in a phosphoinositide 3-kinase (PI 3-kinase)–dependent manner in vivo in human embryonic kidney (293) cells. All members of the PKC family tested formed complexes with PDK1. PDK1-dependent phosphorylation of PKCδ in vitro was stimulated by combined PKC and PDK1 activators. The activation loop phosphorylation of PKCδ in response to serum stimulation of cells was PI 3-kinase–dependent and was enhanced by PDK1 coexpression.