Current Biology
Volume 8, Issue 19, 24 September 1998, Pages 1049-1057
Journal home page for Current Biology

Research Paper
Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2

https://doi.org/10.1016/S0960-9822(98)70442-7Get rights and content
Under an Elsevier user license
open archive

Abstract

Background: Mitogen-activated protein (MAP) kinases (or extracellular signal regulated kinases; Erks) and stress-activated protein (SAP) kinases mediate cellular responses to a wide variety of signals. In the Erk MAP kinase pathway, activation of MAP kinases takes place in the cytoplasm and the activated enzyme moves to the nucleus. This translocation to the nucleus is essential to MAP kinase signalling because it enables the kinase to phosphorylate transcription factors. Whether components of the pathway mediated by the SAP kinase p38 change their cellular location on activation is not clear; we have therefore studied the cellular localisation of components of this pathway before and after stimulation.

Results: The p38 SAP kinase substrate MAP-kinase-activated protein kinase-2 (MAPKAP kinase-2) contains a putative nuclear localisation signal which we show is functional and required for activation by a variety of stimuli. Following phosphorylation of MAPKAP kinase-2, nuclear p38 was exported to the cytoplasm in a complex with MAPKAP kinase-2. Export of MAPKAP kinase-2 required phosphorylation by p38 but did not appear to require the kinase activity of MAPKAP kinase-2. The p38 activators MKK3 and MKK6 were present in both the nucleus and the cytoplasm, consistent with a role in activating p38 in the nucleus.

Conclusions: In the p38 SAP kinase pathway, MAPKAP kinase-2 serves both as an effector of p38 by phosphorylating substrates and as a determinant of cellular localisation of p38. Nuclear export of p38 and MAPKAP kinase-2 may permit them to phosphorylate substrates in the cytoplasm.

Cited by (0)

R Ben-Levy, S Hooper, R Wilson, HF Paterson and CJ Marshall, CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.

Present address for R Ben-Levy, Prochon Biotech, Building 12, Kiryat Weizmann, Science Park, PO Box 1482, Rehovot 76114, Israel.

R B-Levy, S Hooper and R Wilson contributed equally to this work.

E-mail address for CJ Marshall (corresponding author): [email protected].