Tyrosine Kinases And Phosphatases In Cell Cycle Checkpoint Responses
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
In order for an organism to grow and develop, the cells that make up the tissues and organs need to undergo a process of cellular division, wherein individual cells grow and then divide into two cells. During this process of cellular growth and division the entire genome needs to be duplicated (this occurs during S-phase) and then divided equally into the two daughter cells. In S-phase several so-called 'checkpoint' mechanisms exist which ensure that this occurs in an orderly and precise manner. ....In order for an organism to grow and develop, the cells that make up the tissues and organs need to undergo a process of cellular division, wherein individual cells grow and then divide into two cells. During this process of cellular growth and division the entire genome needs to be duplicated (this occurs during S-phase) and then divided equally into the two daughter cells. In S-phase several so-called 'checkpoint' mechanisms exist which ensure that this occurs in an orderly and precise manner. The so-called 'DNA replication checkpoint' delays S-phase progression in response to 'replication stresses' that may otherwise cause DNA damage. Protein tyrosine kinases (PTKs) are hyperactivated in many human solid tumours and blood malignancies contributing to varied aspects of tumour progression. Our preliminary studies indicate that the inactivation of PTKs by protein tyrosine phosphatases may be essential for the suppression of S-phase progression in response to replication stress. Our goal is to understand the molecular mechanisms by which PTKs and tyrosine phosphatases contribute to S-phase checkpoints. Our studies will provide important insights into DNA replication stress-induced checkpoint responses in mammals and identify unprecedented mechanisms by which hyperactivated PTKs may contribute to tumour development.Read moreRead less
Protein Tyrosine Phosphatases In The Regulation Of Insulin Receptor Signalling And Glucose Uptake
Funder
National Health and Medical Research Council
Funding Amount
$425,250.00
Summary
The key pathological feature of type II diabetes is the lack of cellular response to normal levels of circulating insulin. Insulin binding to its cell surface transmembrane receptor initiates a cascade of events known as cellular signalling that results in amongst other things in the uptake of glucose. Protein tyrosine phosphatases (PTPs) are key negative regulators of insulin-induced signalling events and their inhibition with broad based chemical inhibitors can mimic several actions of insulin ....The key pathological feature of type II diabetes is the lack of cellular response to normal levels of circulating insulin. Insulin binding to its cell surface transmembrane receptor initiates a cascade of events known as cellular signalling that results in amongst other things in the uptake of glucose. Protein tyrosine phosphatases (PTPs) are key negative regulators of insulin-induced signalling events and their inhibition with broad based chemical inhibitors can mimic several actions of insulin and lower blood glucose levels in both normal and diabetic rats. This proposal will examine the roles of PTPs and in particular TCPTP and PTP1B in insulin receptor-mediated signalling and glucose uptake. Moreover we will explore the role of TCPTP in alternate insulin receptor-independent processes for glucose uptake. Our studies will shed light on processes important for the regulation of glucose uptake. Moreover our studies may lead to the development of drugs capable of inhibiting PTPs such as TCPTP, that may allow for enhanced glucose uptake and have therapeutic use in the treatment of type II diabetes.Read moreRead less
Regulation And Function Of The Protein Tyrosine Phosphatase TCPTP In Mitosis
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
The cell cycle is a universal process by which cells reproduce and it underlies the growth and development of all living organisms. The most important events of the cell cycle concern the replication of chromosomal DNA during S phase and the separation of replicated DNA into progeny cells at mitosis. Mitosis is morphologically the most dynamic phase of the cell cycle and involves the precise coordination of many processes that are governed by reversible protein phosphorylation. Protein phosphata ....The cell cycle is a universal process by which cells reproduce and it underlies the growth and development of all living organisms. The most important events of the cell cycle concern the replication of chromosomal DNA during S phase and the separation of replicated DNA into progeny cells at mitosis. Mitosis is morphologically the most dynamic phase of the cell cycle and involves the precise coordination of many processes that are governed by reversible protein phosphorylation. Protein phosphatases play an important role in reversible protein phosphorylation and they are essential for mitosis. This grant proposal is focused on understanding the regulation and function of protein phosphatases in mitosis. Our studies will provide novel insight into processes mediating mitosis and may lead to the development of alternative strategies for treating cancer.Read moreRead less