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The ERK/MAPK cascade is a central signaling pathway that regulates various cellular processes including proliferation and differentiation.A hallmark of this cascade is the transmission of extracellular signals into the nucleus in order to induce the transcription of various genes.This is mediated in part by a direct translocation of ERKs into the nucleus.However, despite the importance of this process very little is known about the molecular mechanisms of ERKs translocation, as ERKs do not contain a nuclear localization signal and do not interact with any known nuclear shuttling protein.In the course of studying the structure-function relationships of ERKs we identified a three aminoacid domain (Ser-Pro-Ser; SPS domain) that participates in both non-regulated and facilitated nuclear translocation of these proteins.