PROTEIN-KINASE-C ISOTYPES CONTROLLED BY PHOSPHOINOSITIDE 3-KINASE THROUGH THE PROTEIN-KINASE PDK1

Phosphorylation sites in members of the protein kinase A (PKA), PKG, a nd PKC kinase subfamily are conserved. Thus, the PKB kinase PDK1 may b e responsible for the phosphorylation of PKC isotypes. PDK1 phosphoryl ated the activation Loop sites of PKC zeta and PKC delta 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 t ested formed complexes with PDK1, PDK1-dependent phosphorylation of PK C delta in vitro was stimulated by combined PKC and PDK1 activators. T he activation Loop phosphorylation of PKC delta in response to serum s timulation of cells was PI 3-kinase-dependent and was enhanced by PDK1 coexpression.