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Signaling genomics with a functional library of the Ras superfamily of human small GTPases
- Date/Time : Wed March 26., 2003
- Speaker : Dr. Won Do Heo
- Department of Molecular Pharmacology, Stanford
- Place : Life Science Bldg. #104
- For inquires : Professor Inhwan Hwang Dept. of Life Science
생명과학과 황인환 교수 (☎279-2128)
The proteome of mammalian cells is largely built from protein families with individual members carrying out specific cellular tasks. We took the Ras superfamily of small GTPases and investigated subcellular localization of wild-type, constitutively active, and dominant negative forms of 140 human small GTPases in HeLa, NIH3T3, and Swiss 3T3 cells. We also investigated the activation of PIP3 production by each human small GTPase. Expression of a representative set of one hundred constitutively active human small GTPases induced cell morphologies that fell into nine distinct classes. An algorithm was developed that uses this functional class assignment to identify function specific amino acids. For the example of Rac1, which induces lamellipodia, and CDC42, which induces filopodia, five dispersed amino acids were identified that were not predictable from available structural data. CDC42 and Rac mutated at these sites had a true switch of function characteristic. Our study introduces a strategy to dissect the complex cellular roles of protein families by classifying functional responses and identifying the critical sites on protein surfaces responsible for functional selectivity.