Fig. 8. Proposed model for the nucleo-cytoplasmic shuttling of p42/p44 MAPKs. During stimulation, p42/p44 MAPKs localization and activity are regulated in three phases: (1) in quiescent cells, p42/p44 MAPKs are fully inactive and mainly located in the cytoplasm, sequestered by their interaction with MEK; (2) after 5 minutes of stimulation (mitogenic or not) there is a massive entry of activated p42/p44 MAPKs into the nucleus; (3) after 3 hours of mitogenic stimulation, p42/p44 MAPKs accumulate massively in the nucleus bound in an inactive form to nuclear anchors. Active forms of p42/p44 MAPKs are represented in red and inactive forms are shown in green.