Mechanisms regulating the nuclear translocation of p38 MAP kinase.
p38 mitogen-activated protein kinase (MAPK) is of fundamental importance in a cell's response to environmental stresses, cytokines and DNA damage. p38 resides in the cytoplasm of resting cells, and translocates into the nucleus upon activation, yet the exact mechanisms remain largely unclear. We show here that the phosphorylation-dependent nuclear translocation of p38 is a common phenomenon when cells are stimulated with various stresses. On the other hand, the nuclear export of p38 requires its dephosphorylation, and it is exported both in a MK2-dependent and a nuclear export signal (NES)-independent manner. Although different p38-regulated/activated protein kinase (PRAK) mutants all dictate the intracellular localization of p38, results from a PRAK-deficient cell line indicate that it plays no role in this process. Microtubule depolymerizing reagent nocodazole and dynein inhibitor EHNA both block the nuclear translocation of p38, demonstrating roles for microtubules and dynein in p38 transport. Taken together, stress-induced nuclear accumulation of p38 is a phosphorylation-dependent, microtubule- and dynein-associated process.
Gong
Xiaowei
X
Department of Pathophysiology, Key Laboratory of Proteomics of Gongdong Province, Southern Medical University, Guangzhou 510515, China. gongxw@fimmu.com
Ming
Xiaoyan
X
Deng
Peng
P
Jiang
Yong
Y
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D018053:Arsenites / Q000494:pharmacology; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D004398:Dyneins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D041681:NIH 3T3 Cells; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D050257:Tubulin Modulators / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000099190:MAP-Kinase-Activated Kinase 2
D000225:Adenine; D018053:Arsenites; D004398:Dyneins; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015739:Nocodazole; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D050257:Tubulin Modulators; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C010192:9-(2-hydroxy-3-nonyl)adenine; C111049:MAP-kinase-activated kinase 5; C015001:arsenite