Inositol phosphates and phosphoinositides, respectively soluble and lipidic molecules, play a fundamental role in cell regulation and membrane dynamics. Phosphatidylinositol, a membrane phospholipid, can be reversibly phosphorylated at the 3, 4 and 5 positions of myo-inositol to generate phosphoinositides (PIs) (seven are currently known in mammalian cells). Phosphoinositides play a fundamental role in cell physiology, signalling and physiopathology. Our interest in this metabolism started with the cloning of a series of inositol polyphosphate 5-phosphatase and Ins(1,4,5)P3 3-kinases. On the phosphatase side, this led us to clone the SH2 domain containing inositol 5-phosphatase SHIP1 and SHIP2. The substrate of SHIP1/2 is PI(3,4,5)P3 and the product of the reaction is PI(3,4)P2. Both PIs are able to bind to PKB and PDK1 PH domains and to facilitate PDK1 phosphoylation of PKB. SHIP1/2 are very much studied due to their implication in immune response, myeloid cell survival for SHIP1 and insulin signalling and the control of obesity for SHIP2. In addition, there is good evidence of SHIP1/2 implication in human cancer and growth factor signalling.
The general goal of our laboratory is to understand why and how phosphatases and kinases that act on inositol phosphates and phosphoinositides are critical in signalling.
A list of publications of the lab can be found in http://publicationslist.org/christophe-erneux.