title: AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation.
abstract: The protein kinase Akt/PKB is activated via a multistep process by a variety of signals. In the early steps of this process, PI-3 kinase-generated D3-phosphorylated phosphoinositides bind the Akt PH domain and induce the translocation of the kinase to the plasma membrane where it co-localizes with phosphoinositide-dependent kinase-1. By binding to the PH domains of both Akt and phosphoinositide-dependent kinase-1, D3-phosphorylated phosphoinositides appear to also induce conformational changes that permit phosphoinositide-dependent kinase-1 to phosphorylate the activation loop of Akt. The paradigm of Akt activation via phosphoinositide-dependent phosphorylation provided a framework for research into the mechanism of activation of other members of the AGC kinase group (p70S6K, PKC, and PKA) and members of the Tec tyrosine kinase family (TecI, TecII, Btk/Atk, Itk/Tsk/Emt, Txk/Rlk, and Bm/Etk). The result was the discovery that these kinases and Akt are activated by overlapping pathways. In this review, we present our current understanding of the regulation and function of the Akt kinase and we discuss the common and unique features of the activation processes of Akt and the AGC and Tec kinase families. In addition, we present an overview of the biosynthesis of phosphoinositides that contribute to the regulation of these kinases.
authors.affiliation: Kimmel Cancer Institute, Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: T O
authors.initials: TO
authors.lastname: Chan
authors.forename: S E
authors.initials: SE
authors.lastname: Rittenhouse
authors.forename: P N
authors.initials: PN
authors.lastname: Tsichlis
mesh_terms: D000595:Amino Acid Sequence; D004789:Enzyme Activation; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D010716:Phosphatidylinositols; D017346:Protein Serine-Threonine Kinases