title: AH/PH domain-mediated interaction between Akt molecules and its potential role in Akt regulation.
abstract: The cytoplasmic serine-threonine protein kinase coded for by the c-akt proto-oncogene features a protein kinase C-like catalytic domain and a unique NH2-terminal domain (AH domain). The AH domain is a member of a domain superfamily whose prototype was observed in pleckstrin (pleckstrin homology, or PH, domain). In this communication, we present evidence that the AH/PH domain is a domain of protein-protein interaction which mediates the formation of Akt protein complexes. The interaction between c-akt AH/PH domains is highly specific, as determined by the failure of this domain to bind AKT2. The AH/PH domain-mediated interactions depend on the integrity of the entire domain. Akt molecules with deletions of the NH2-terminal portion (amino acids 11 to 60) and AH/PH constructs with deletions of the C-terminal portion of this domain (amino acids 107 to 147) fail to interact with c-akt. To determine the significance of these findings, we carried out in vitro kinase assays using Akt immunoprecipitates from serum-starved and serum-starved, platelet-derived growth factor-stimulated NIH 3T3 cells. Addition of maltose-binding protein-AH/PH fusion recombinant protein, which is expected to bind Akt, to the immunoprecipitates from serum-starved cells induced the activation of the Akt kinase.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
authors.forename: K
authors.initials: K
authors.lastname: Datta
authors.forename: T F
authors.initials: TF
authors.lastname: Franke
authors.forename: T O
authors.initials: TO
authors.lastname: Chan
authors.forename: A
authors.initials: A
authors.lastname: Makris
authors.forename: S I
authors.initials: SI
authors.lastname: Yang
authors.forename: D R
authors.initials: DR
authors.lastname: Kaplan
authors.forename: D K
authors.initials: DK
authors.lastname: Morrison
authors.forename: E A
authors.initials: EA
authors.lastname: Golemis
authors.forename: P N
authors.initials: PN
authors.lastname: Tsichlis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt