Phosphoinositide 3-kinase gamma has multiple phospholipid binding sites.
Phosphoinositide 3-kinase gamma is a multifunctional enzyme with lipid and protein kinase activities that also acts as a scaffold protein in many diverse signalling processes. The enzyme contains five different domains, but their individual contributions to membrane binding are not fully understood. Here, using in vitro liposome binding assays of individual domains and deletion constructs of human phosphoinositide 3-kinase gamma, we show that each domain is capable of binding anionic phospholipids to varying degrees, depending on the charge of the anionic substrate. Moreover, with the exception of the C2-domain, deletion of any single protein domain results in a complete loss of kinase activity toward both lipids and proteins.
Schmidt
Carsten
C
Universitätsklinikum Jena, Institut für Biochemie II, Nonnenplan 2, 07740, Jena, Germany. carsten.schmidt1@mti.uni-jena.de
Schilli-Westermann
Margret
M
Klinger
Reinhard
R
Kirsch
Cornelia
C
D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D058544:Class Ib Phosphatidylinositol 3-Kinase; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D000838:Anions; D007527:Isoenzymes; D008081:Liposomes; D010743:Phospholipids; D019869:Phosphatidylinositol 3-Kinases; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546760:PIK3CG protein, human