CYTOPLASMIC LOCALIZATION OF MITOGEN-ACTIVATED PROTEIN-KINASE KINASE DIRECTED BY ITS NH2-TERMINAL, LEUCINE-RICH SHORT AMINO-ACID-SEQUENCE, WHICH ACTS AS A NUCLEAR EXPORT SIGNAL

Mitogen-activated protein kinase (MAPK) is activated in cytoplasm in r esponse to extracellular signals and then is translocated to nucleus. A directed activator for MAPK, MAPK kinase (MAPKK), stays in cytoplasm to transmit the signal from the plasma membrane to MAPK. Here we show that MAPK contains a short amino acid sequence in the N-terminal regi on (residues 32-44), which acts as a nuclear export signal (NES) and t hus is required for cytoplasmic localization of MAPKK. This NES sequen ce of MAPKK, like that of protein kinase inhibitor of cAMP-dependent p rotein kinase or Rev, is rich in leucine residues, which are crucial f or the NES activity. Furthermore, the NES peptide of protein kinase in hibitor, as well as the NES peptide of MAPKK, inhibited the nuclear ex port of ovalbumin conjugated to the NES peptide of MAPKK. These result s may suggest a common mechanism of nuclear export using a general leu cine-rich NES.