Anionic phospholipids are involved in membrane targeting of PI 3-kinase gamma.
Phosphoinositide 3-kinases (PI 3-kinases) have critical roles in diverse cellular signaling processes and in protein trafficking. In contrast to the class I PI 3-kinases alpha, beta, and delta which bind via src homology 2 (SH2) domains of adaptor proteins to tyrosine kinase receptors, the mechanism of recruitment of the PI 3-kinase gamma to membranes is unknown. We report in vitro experiments using immobilized proteins and small unilamellar vesicles which suggest an involvement of anionic phospholipids in membrane association of PI 3-kinase gamma. Furthermore we provide evidence that the enzyme displays beside the catalytic center a phospholipid binding domain which is essential for enzyme activity.
Kirsch
C
C
Institute of Biochemistry II, Medical Faculty, University of Jena, Nonnenplan 2, Jena, D-07740, Germany.
Wetzker
R
R
Klinger
R
R
D000818:Animals; D000838:Anions; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism*; D058544:Class Ib Phosphatidylinositol 3-Kinase; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008081:Liposomes; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism*; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D000838:Anions; D007527:Isoenzymes; D008081:Liposomes; D008563:Membrane Lipids; D010743:Phospholipids; D011993:Recombinant Fusion Proteins; D019869:Phosphatidylinositol 3-Kinases; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546760:PIK3CG protein, human