Sci. Signal., 3 December 2013
Target Upstream of Oncogenic RasMembers of the K-Ras family of small guanosine triphosphatases mediate signaling by cytokine and growth factor receptors to activate extracellular signal–regulated kinase (ERK), leading to cellular proliferation. Mutant K-Ras molecules, for example, K-RasG12D, accumulate in the active form and are associated with certain leukemias. Through flow cytometric analysis of phosphorylated proteins in mouse bone marrow cells, Diaz-Flores et al. showed that ERK activation downstream of K-RasG12D required cytokine receptor–dependent activation of phospholipase C– (PLC-) and phosphoinositide 3-kinase (PI3K) signaling. Treatment of mice with a clinically available PI3K inhibitor reduced ERK activation in cells expressing K-RasG12D, suggesting that molecules upstream of oncogenic Ras may provide therapeutic targets against some cancers.
Citation: E. Diaz-Flores, H. Goldschmidt, P. Depeille, V. Ng, J. Akutagawa, K. Krisman, M. Crone, M. R. Burgess, O. Williams, B. Houseman, K. Shokat, D. Sampath, G. Bollag, J. P. Roose, B. S. Braun, K. Shannon, PLC- and PI3K Link Cytokines to ERK Activation in Hematopoietic Cells with Normal and Oncogenic Kras. Sci. Signal. 6, ra105 (2013).
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