Signalling mechanisms of the ShcD adaptor protein

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Signal transduction is a central process in multicellular organisms that allows for the exchange of informational cues between and within cells. These cues are interpreted by organized networks of protein interactions inside the cell which regulate complex biochemical events, ultimately converting them into biological responses such as growth, migration, differentiation and survival. Cells have evolved a tremendous ability to selectively activate specific downstream pathways, through formation of distinct protein complexes. Understanding the molecular basis of these interactions is therefore a significant challenge in biology. The Shc family of intracellular adaptor proteins provides a unique opportunity to investigate the questions of selectivity and specificity. These proteins function to relay phosphotyrosine-based signals from cell surface receptors to various effector proteins, and they play critical roles in cardiovascular and neural development. Intriguingly, the Shc family has increased in complexity from one gene in flies to several in mammals, and we have recently characterized a fourth mammalian homolog, ShcD. We have found that this adaptor is unique among Shc proteins in its expression pattern and its ability to associate with binding targets, supporting the notion that elaborate diversification of Shc functions has occurred during evolution. Using a combination of biochemical, cellular and genetic approaches, we propose to identify the molecular components and biological functions associated with ShcD. The goal of this study is to dissect the Shc protein signaling paradigm to reveal the mechanisms by which specificity in signal transduction has evolved from a single family of simple adaptor proteins. Our findings may also provide mechanistic insight to explain how perturbations in cellular communication can lead to altered cell function.