Cells integrate internal and external stimuli through complex signaling pathways in order to adapt to changing environments. In particular, cells must know when to grow and when not to. In the phosphoinositide 3-kinase (PI3K) pathway downstream of growth factors, Sgk3 is activated by the signaling lipid PI3P, but the precise mechanism of its activation is unknown. In work published in the Journal of Biological Chemistry, the lab of Thomas Leonard has discovered that Sgk3 is locally activated on membranes by PI3P. In the absence of PI3P, its membrane binding domain maintains Sgk3 in an inactive conformation. Since Sgk3 is upregulated in some cancers, its autoinhibited conformation represents a novel therapeutic target.
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