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The conventional view of cytokine signaling is that receptors transmit information to the nucleus without leaving the plasma membrane. However, accumulating data suggest that some membrane receptors may signal by dissociating from the plasma membrane and translocating to the nucleus, where they direct the transcriptional machinery. One example is the growth hormone receptor (GHR), which has been observed in the nuclei of various normal and neoplastic tissues. Waters and colleagues now present new mechanistic data describing how GHR might localize to the nucleus and influence gene transcription. These findings may have implications for the way we think about cytokine signaling.