 We previously reported that nuclear translocation is essential for p42/p44 MAPKs (ERKs) mitogenic signaling.     ///    "Hence, the nucleus is a critical site for mitogenic signal termination by: (1) nuclear sequestration of p42/p44 MAPKs away from MEK, their cytoplasmic activator. "    ///    "In addition, p42/p44 MAPKs permanently shuttle between the cytoplasm and the nucleus in quiescent as well as in serum stimulated cells. "    ///    "Here we show that, during long-term stimulation, p42/p44 MAPKs become inactive while they accumulate in the nucleus. "    ///    "The phosphatases responsible for p42/p44 MAPKs nuclear inactivation are neo-synthesized, show tyrosine or dual specificity, and interact with p42/p44 MAPKs via a specific docking site. "    ///    "This inactivation was monitored by phospho-specific immunostaining and dephosphorylation of a nuclear p42/p44 MAPKs substrate, HIF-1 alpha. "