TI - Primary structure , tissue distribution , and expression of mouse phosphoinositide -dependent protein kinase -1 , a protein kinase that phosphorylates and activates protein kinase Czeta . AB - Phosphoinositide-dependent protein kinase-1 ( PDK1 ) is a recently identified serine/threonine kinase that phosphorylates and activates Akt and p70 (S6K) , two downstream kinases of phosphatidylinositol 3-kinase . To further study the potential role of PDK1 , we have screened a mouse liver cDNA library and identified a cDNA encoding the enzyme . The predicted mouse PDK1 ( mPDK1 ) protein contained 559 amino acids and a COOH-terminal pleckstrin homology domain . A 7-kilobase mPDK1 mRNA was broadly expressed in mouse tissues and in embryonic cells . In the testis , a high level expression of a tissue -specific 2-kilobase transcript was also detected . Anti-mPDK1 antibody recognized multiple proteins in mouse tissues with molecular masses ranging from 60 to 180 kDa . mPDK1 phosphorylated the conserved threonine residue (Thr402) in the activation loop of protein kinase C-zeta and activated the enzyme in vitro and in cells . Our findings suggest that there may be different isoforms of mPDK1 and that the protein is an upstream kinase that activates divergent pathways downstream of phosphatidylinositol 3-kinase .