title: Structure and function of phosphatidylinositol-3,4 kinase.
abstract: Activation of phosphatidylinositol (PI)-kinase is involved in the regulation of a wide array of cellular activities. The enzyme exists as a dimer, consisting of a catalytic and a regulatory subunit. Five isoforms of the regulatory subunit have been identified and classified into three groups comprising respectively 85-kDa, 55-kDa, and 50-kDa proteins. Structural differences in the N-terminal regions of the different group members contribute to defining their binding specificity, their subcellular distributions, and their capacity to activate the 110-kDa catalytic subunit. Two widely distributed isoforms of the catalytic subunit have been identified-p110alpha and p110beta. Despite the fact that they bind to the p85alpha regulatory subunit similarly, p110alpha and p110beta appear to have separate functions within cells and to be activated by different stimuli. Moreover, although p85/p110 PI-kinase almost exclusively phosphorylates the D-3 position of the inositol ring in phosphoinositides when purified PI is used as a substrate in vitro, it appears to phosphorylate the D-4 position with similar or higher efficiency in vivo. Thus, it is highly probable that p85/p110 PI-kinase transmits signals to downstream targets via both D-3- and D-4-phosphorylated phosphoinositides.
authors.affiliation: The Institute for Adult Disease, Asahi Life Foundation 1-9-14, Nishi-Shinjuku, Shinjuku-Ward, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Funaki
authors.forename: H
authors.initials: H
authors.lastname: Katagiri
authors.forename: K
authors.initials: K
authors.lastname: Inukai
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: T
authors.initials: T
authors.lastname: Asano
mesh_terms: D000818:Animals; D058543:Class Ia Phosphatidylinositol 3-Kinase; D006801:Humans; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D013329:Structure-Activity Relationship
chemical_list: D007527:Isoenzymes; D010716:Phosphatidylinositols; D019869:Phosphatidylinositol 3-Kinases; D058543:Class Ia Phosphatidylinositol 3-Kinase