The role of the 72 kDa inositol polyphosphate 5-phosphatase in cellular function.

Funded Activity Summary

Cells respond to external signals and the environment to undergo cell growth, secretion and-or other specialized functions including control of cell death and-or cell size. We have identified a new enzyme (72kDa 5-phosphatase) which resides inside the cell and regulates signals generated by an enzyme called PI3-kinase. Two of the PI3-kinase signals have been demonstrated to regulate the activity of an oncogene involved in breast and ovarian cancer. We aim to determine the specific role each of these PI3-kinase signals plays in the activation of the oncogene. In addition the levels of the 72kDa enzyme is altered in some cervical and lymphoma cancers. We will image live cells containing specific fluorescent probes under different conditions and study the activation and location of these probes in order to understand how different PI3-kinase signals are regulated in time and space. In addition to regulating signals that are involved in cancer, PI3-kinase controls signals that are important for proper immune function. Phagocytosis is a biological process where specialised immune cells (macrophages) take up and remove harmful particles such as bacteria or tumour cells from the circulation. This process depends on PI3-kinase and the signals it produces. We will determine whether the 72 kDa enzyme, which is expressed in macrophages, plays a role in regulating these signals during phagocytosis. We have shown that the 72 kDa enzyme can interact with several different proteins which may affect its location and activity within the cell. We will examine the effect of these interactions on the PI3-kinase signals which are involved in cell survival and immune responses. We will study the function of the enzyme in the intact animal by producing mice which lack this enzyme. Given the possible role of this enzyme in cancer, these mice will be examined for their susceptibility to develop tumours.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $549,196.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

cancer | cancer mechanisms of growth | cell signaling | cell survival | gene knockout | invasion and metastasis | macrophage | macrophage activation | membrane signaling | phosphoinositide 3-kinase

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