Extracellular-Regulated protein Kinases (ERK), the focus of my PhD studies, functions as the downstream component of the Receptor tyrosine kinase-Ras-Raf-MEK cascade. This cascade is responsible for numerous physiological processes such as cell cycle, proliferation, migration, and differentiation. Importantly, this cascade is overactive in most cancer types but no oncogenic or activating mutations were found in Erk molecules themselves. Therefore, it is of importance to understand the function of Erks in cancer and to answer whether Erks are proto-oncogenes. If the premise that the pathogenicity of the RTK/Ras/Raf/MEK pathway is mediated via Erks is correct, then exclusive activation of Erks should be sufficient to impose similar effects as activation of the entire pathway. In order to address this critical hypothesis, one should be able to activate Erks exclusively in a Mek independent manner and, more importantly, without activating parallel cascades that are commonly activated together with Erks.
Only recently, it became possible to address the question of whether Erks could be oncoproteins owing to the development of a few intrinsically active variants of Erks in our lab. Indeed, one of the mutations that render Erks intrinsically active catalytically also bestowed oncogenic properties on Erk1, as it was able to transform mammalian cells in culture and to give rise to tumors in Drosophila.
The question is still open therefore, whether our intrinsically active Erk, could give rise to tumors in the context of the mammalian organism. One major goal of my PhD studies, is to provide an explicit answer to this question by establishing a transgenic mice system in which expression of active Erk1 is induced in a tissue-specific manner.