Scholar Profile

Linda A. Hicke

Dean
College of Natural Sciences
The University of Texas at Austin
1 University Station G2500
Austin, YX 78712
Voice: 512-471-3285
Personal Homepage
1998 Searle Scholar

Research Interests

Down Regulation of Signal Transducing Receptors

Cells receive information from their environment and neighboring cells via extracellular molecules, such as growth factors and hormones, that bind to specific cell surface receptors. The binding of ligand to its receptor activates a signal transduction pathway that allows the cell to respond to the stimulus. However, once cells act upon a signal they must return to their normal, unstimulated state. They do this by down regulating their response to the signal in a variety of different ways, one of which is to inactivate the cell surface receptor itself.

We study how receptors are down regulated after ligand-binding. One of the key events in receptor down regulation is the modification of the receptor's cytoplasmic tail with the small peptide ubiquitin. Receptor ubiquitination triggers removal of the protein from the cell surface by endocytosis which leads to transport of the protein to the lysosome. In the lysosome the protein is degraded by proteases and thus permanently inactivated.

In our laboratory we take advantage of the ability to use genetics, biochemistry, and cell biology in yeast to investigate the down regulation of the mating pheromone receptors of Saccharomyces cerevisiae. A variety of mammalian receptors also undergo ubiquitin-dependent down regulation and therefore we use yeast and animal cells to address 1) the mechanism of how ubiquitin stimulates endocytosis of receptors at the molecular level, 2) what different types of receptors undergo ubiquitin-dependent endocytosis, and 3) how ubiquitin acts together with other endocytosis signals to direct an internalized protein to the lysosome rather than back to the cell surface.