Direct Modification and Activation of a Nuclear Receptor–PIP 2 Complex by the Inositol Lipid Kinase IPMK

• DOI: 10.1126/scisignal.2003111
• Publication Date: 2012-06-19T20:13:06Z
• Authors: Raymond D. Blind; Miyuki Suzawa; Holly A. Ingraham
• Keywords: Phosphatidylinositol 4,5-bisphosphate

Phosphatidylinositol 4,5-bisphosphate (PIP₂) is best known as a plasma membrane-bound regulatory lipid. Although PIP₂ and phosphoinositide-modifying enzymes coexist in the nucleus, their nuclear roles remain unclear. We showed that inositol polyphosphate multikinase (IPMK), which functions both an kinase phosphoinositide 3-kinase (PI3K), interacts with receptor steroidogenic factor 1 (SF-1) phosphorylates its bound ligand, PIP₂. In vitro studies was not phosphorylated by IPMK if displaced or blocked from binding to large hydrophobic pocket of SF-1 ability phosphorylate specific did occur type p110 PI3Ks. IPMK-generated SF-1-PIP₃ (phosphatidylinositol 3,4,5-trisphosphate) dephosphorylated lipid phosphatase PTEN. Consistent activities PTEN on SF-1-PIP(n), transcriptional activity reduced silencing overexpressing This kinases phosphatases directly remodel alter non-membrane protein-lipid complex establishes previously unappreciated pathway for promoting lipid-mediated signaling nucleus.