The stereoselective recognition of substrates by phosphoinositide kinases.

  1. Macphee, C.H. 2
  2. Carter, A.N. 2
  3. Ruiz-Larrea, F. 1
  4. Ward, J.G. 2
  5. Young, R.C. 2
  6. Downes, C.P. 3
  1. 1 Ludwig Cancer Research
    info

    Ludwig Cancer Research

    Oxford, Reino Unido

    ROR https://ror.org/01e473h50

  2. 2 SmithKline Beecham Pharmaceuticals, Frythe, Welwyn, Hertfordshire AL6 9AR, United Kingdom
  3. 3 University of Dundee
    info

    University of Dundee

    Dundee, Reino Unido

    ROR https://ror.org/03h2bxq36

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Revista:
Journal of Biological Chemistry (Print)

ISSN: 0021-9258

Año de publicación: 1992

Volumen: 267

Número: 16

Páginas: 11137-11143

Tipo: Artículo

PMID: 1317855 SCOPUS: 2-s2.0-0026661575 GOOGLE SCHOLAR

Otras publicaciones en: Journal of Biological Chemistry (Print)

Repositorio institucional: lock_openAcceso abierto Editor

Resumen

Soluble phosphatidylinositol (PtdIns) 4- and 3-kinase activities were partially purified and characterized from human placental extracts. The placental PtdIns 4-kinase (type 3) has a K(m) for ATP of 460 μM and is kinetically different to a partially purified human erythrocyte, membrane- bound, PtdIns 4-kinase (type 2). These three inositol lipid kinases were then used to compare their substrate specificities against the four synthetic stereoisomers of dipalmitoyl PtdIns. Only the placental 4-kinase was influenced by the chirality of the glycerol moiety of PtdIns. However, neither of the 4-kinases was able to phosphorylate. L-PtdIns and, therefore, these kinases have an absolute requirement for the inositol ring to be linked to the glyceryl backbone of the lipid through the D-1 position. Phosphoinositide 3-kinase, on the other hand, was found to phosphorylate both D- and L-PtdIns. While the 3-kinase phosphorylated exclusively the D-3 position of D-PtdIns, further analyses demonstrated that the same enzyme phosphorylated two sites on L-PtdIns, namely the D-6 and D-5 positions of the inositol ring. Some implications of these findings are discussed.