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Interaction of MAP kinase with MAP kinase kinase: its possible role in the control of nucleocytoplasmic transport of MAP kinase
Author(s) -
Fukuda Makoto,
Gotoh Yukiko,
Nishida Eisuke
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.8.1901
Subject(s) - mapk/erk pathway , microbiology and biotechnology , biology , mitogen activated protein kinase kinase , map kinase kinase kinase , mitogen activated protein kinase 3 , protein kinase a , cytoplasm , kinase , mitogen activated protein kinase , mapk cascade
The mitogen‐activated protein kinase (MAPK) cascade consisting of MAPK and its direct activator, MAPK kinase (MAPKK), is essential for signaling of various extracellular stimuli to the nucleus. Upon stimulation, MAPK is translocated to the nucleus, whereas MAPKK stays in the cytoplasm. It has been shown recently that the cytoplasmic localization of MAPKK is determined by its nuclear export signal (NES) in the near N‐terminal region (residues 33–44). However, the mechanism determining the subcellular distribution of MAPK has been poorly understood. Here, we show that introduction of v‐Ras, active STE11 or constitutively active MAPKK can induce nuclear translocation of MAPK in mammalian cultured cells. Furthermore, we show evidence suggesting that MAPK is localized to the cytoplasm through its specific association with MAPKK and that nuclear accumulation of MAPK is accompanied by dissociation of a complex between MAPK and MAPKK following activation of the MAPK pathway. We have identified the MAPK‐binding site of MAPKK as its N‐terminal residues 1–32. Moreover, a peptide encompassing the MAPK‐binding site and the NES sequence of MAPKK has been shown to be sufficient to retain MAPK to the cytoplasm. These findings reveal the molecular basis regulating subcellular distribution of MAPK, and identify a novel function of MAPKK as a cytoplasmic anchoring protein for MAPK.