The regulation of pleiotropic responses by phospho-Ser/Tyr binary switches embedded in growth factor receptors

Funded Activity Summary

Cells in the body are able to accomplish an impressive range of functions within their lifetime. Underlying this diversity in cellular functions are a quorum of fundamental cellular responses that include cell survival, cell proliferation (growth) and cell differentiation (commitment to a more mature cell identity). Diffusible factors (called growth factors) are important in regulating these cellular responses. This is achieved through growth factor binding to specific proteins (called receptors) on the surface of cells which in turn activate signalling cascades that convey messages within the cell instructing a specific response. We have identified a new mechanism that allows a growth factor receptor to convert analogue inputs (in the form of growth factor stimulation) to a digital output (where a cell responds in a decisive fashion). This analogue-to-digital conversion is encoded by a molecular switch embedded in growth factor receptors that toggles between two alternate positions to promote either cell survival alone or cell survival as well as cell differentiation-proliferation. In this manner, these molecular switches have binary (either-or) characteristics and provide a new explanation for the independent regulation and coordination of different cell functions. These findings have implications for understanding how specific cellular responses such as cell survival, proliferation and differentiation can be regulated and perhaps harnessed to improve tissue regeneration after damage (e.g. in stroke, heart attack trauma) or in understanding how things go wrong in diseases such as cancer where cell survival, proliferation and differentiation become deregulated

Funded Activity Details

Start Date: 01-01-2006

End Date: 01-01-2008

Funding Scheme: NHMRC Project Grants

Funding Amount: $349,190.00

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

angiogenesis | cancer | cell surface receptors | development | fibroblast growth factors | intracellular signal transduction | organogenesis | pleiotropic cellular responses | protein phosphorylation | tissue regeneration

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