title: c-Jun N-terminal kinase phosphorylation of stathmin confers protection against cellular stress.
abstract: The cell stress response encompasses the range of intracellular events required for adaptation to stimuli detrimental to cell survival. Although the c-Jun N-terminal kinase (JNK) is a stress-activated kinase that can promote either cell survival or death in response to detrimental stimuli, the JNK-regulated mechanisms involved in survival are not fully characterized. Here we show that in response to hyperosmotic stress, JNK phosphorylates a key cytoplasmic microtubule regulatory protein, stathmin (STMN), on conserved Ser-25 and Ser-38 residues. In in vitro biochemical studies, we identified STMN Ser-38 as the critical residue required for efficient phosphorylation by JNK and identified a novel kinase interaction domain in STMN required for recognition by JNK. We revealed that JNK was required for microtubule stabilization in response to hyperosmotic stress. Importantly, we also demonstrated a novel cytoprotective function for STMN, as the knockdown of STMN levels by siRNA was sufficient to augment viability in response to hyperosmotic stress. Our findings show that JNK targeting of STMN represents a novel stress-activated cytoprotective mechanism involving microtubule network changes.
authors.affiliation: Department of Biochemistry, Bio21 Institute, University of Melbourne, Parkville, 3010 Victoria, Australia.
authors.forename: Dominic C H
authors.initials: DC
authors.lastname: Ng
authors.forename: Teresa T
authors.initials: TT
authors.lastname: Zhao
authors.forename: Yvonne Y C
authors.initials: YY
authors.lastname: Yeap
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Ngoei
authors.forename: Marie A
authors.initials: MA
authors.lastname: Bogoyevitch
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D009997:Osmotic Pressure / Q000502:physiology; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*
chemical_list: D050777:Stathmin; D048670:MAP Kinase Kinase 4