Research ArticleCancer

PLC-γ and PI3K Link Cytokines to ERK Activation in Hematopoietic Cells with Normal and Oncogenic Kras

Sci. Signal.  03 Dec 2013:
Vol. 6, Issue 304, pp. ra105
DOI: 10.1126/scisignal.2004125

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Target Upstream of Oncogenic Ras

Members 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–γ (PLC-γ) 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.