Understanding how signaling cascades dictate cell fate decisions

 

The signaling pathway connecting RAS and mitogen-activated protein kinases ERK1 and ERK2 is essential for the regulation of cell fate decisions. Therefore, it comes to no surprise that gain of function mutations in constituents of the RAS-ERK pathway are common, appearing in nearly 30-50% of human cancer. Sustained activation of the ERK1/2 pathway contributes to oncogenic transformation, controlling cell survival and proliferation. My work over the years has been focused on understanding how this pathway signals as well as its deregulation in cancer (for more information on this topic click here ).

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In recent years, our lab and others have shown before that in addition to regulating proliferation and survival, ERK2 but not ERK1, also promotes EMT (epithelial-to-mesenchymal transition) and tumor cell motility, invasion and metastasis. These studies also highlight the critical importance of different docking sites on ERK2 and its substrates that mediate the interaction with the kinases in order to provide specificity to signaling pathways. Two types of docking sites have been reported for ERK substrates, the DEF motif, which is present in many nuclear substrates of ERK, and the D-domain, which is important for the interaction between ERK regulators and other kinases, such as RSK (for more information on this topic click here ). In recent years, our lab and others have shown before that in addition to regulating proliferation and survival, ERK2 but not ERK1, also promotes EMT (epithelial-to-mesenchymal transition) and tumor cell motility, invasion and metastasis. These studies also highlight the critical importance of different docking sites on ERK2 and its substrates that mediate the interaction with the kinases in order to provide specificity to signaling pathways. Two types of docking sites have been reported for ERK substrates, the DEF motif, which is present in many nuclear substrates of ERK, and the D-domain, which is important for the interaction between ERK regulators and other kinases, such as RSK

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