Overview:

PDK1 (3-phosphoinositide-dependent protein kinase) is activated by the presence of PtdIns(3,4,5)P3 or PtdIns(3,4)P2 (1). PDK1 then activates protein kinase B (PKB) which, in turn, inactivates glycogen synthase kinase-3 (GSK3). Phosphorylation of other proteins by PKB and GSK3 is likely to mediate many of the intracellular actions of insulin. Thus, PDK1 plays a key role in mediating many of the actions of the second messenger(s) PtdIns(3,4, 5)P3 and/or PtdIns(3,4)P2. The human PDK1 is a 556-residue monomeric enzyme comprising of a catalytic domain that is most similar to the PKA, PKB and PKC subfamily of protein kinases. PDK1 activity is dependent on phosphorylation at Ser241. Other known phosphorylation target sites include Ser25, Ser393, Ser 396 and Ser410 (3).

References:

1. Cohen, P. et al: PDK1, one of the missing links in insulin signal transduction? FEBS Letter. 1997 Jun 23;410(1):3-10. Review.

2. Alessi, DR. et al: Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha. Curr Biol. 1997 Apr 1;7(4):261-9.

3. Casamayor A. et al: Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo. Biochem J. 1999 Sep 1;342 ( Pt 2):287-92.