Regulation of PtdIns(3,4,5)P3 by inositol polyphosphate 5-phosphatases

生长细胞通过分裂和增殖对生长因子作出反应。不受控制的细胞生长会导致癌症。信号在生长因子刺激后从细胞膜释放，通过细胞内信号分子的复杂网络进行通信，指示细胞核分裂。介导细胞生长的一个关键信号网络是磷酸肌醇信使分子。这些信号被称为肌醇多磷酸5-磷酸酶的蛋白质家族关闭。我们认为5-磷酸酶对于细胞的正常生长至关重要。几项研究表明，如果没有它们，可能会发生肿瘤形成。我们已经确定了这个酶家族的一个新成员，称为SHIP-2。该提案旨在研究该酶家族代谢信号分子从而调节细胞生长的机制。我们还将描述5-磷酸酶如何控制原始细胞分化为成熟细胞的正常途径。

Growing cells respond to growth factors by dividing and proliferating. Uncontrolled cell growth leads to cancer. Signals are released from the cell membrane following growth factor stimulation, that communicate via a complex network of intracellular signalling molecules, that instruct the nucleus to divide. One critical signalling network that mediates cell growth are the phosphoinositide messenger molecules. These signals are switched off by a family of proteins called inositol polyphosphate 5-phosphatases. We propose the 5-phosphatases are essential for normal cell growth. Several studies have suggested in their absence tumour formation may occurr. We have identified a new member of this enzyme family called SHIP-2. This proposal aims to investigate the mechanisms by which this enzyme family metabolises signalling molecules and thereby regulates cell growth. We will also characterize how the 5-phosphatases control the normal pathways by which primitive cells differeniate into mature cells.