Differential modulation of the phosphoproteome by the MAP Kinases isoforms p38α and p38β

ABSTRACT: The stress-activated p38 mitogen activated protein kinases (MAPK) mediate responses to osmotic shock, radiation, immune stimuli, inflammatory cues, and many other stresses. These kinases are activated rapidly, within seconds of stress induction, yet, their continuous activation, as commonly happens in inflammations and cancer, induce different signaling cascades than transient activation. This study aimed to follow the specific signaling cascades induced by two of these p38 MAPKs activated by strong and rapid stress, or by continuous (chronic) activations. The analysis was based on large-scale proteomics and phosphoproteomics analyses using SILAC labeling of mouse embryonic fibroblasts (MEF) deficient in each of these p38 kinases, expressing constitutively expressed wildtype p38α or p38β, or their intrinsically active variants. In addition, the effects of anisomycin, inducing strong and rapid stress response, were followed in wildtype MEF or in MEF knocked-out for these p38α or p38β. The signaling events, induced the each p38 during the chronic responses, indicated adaptations of the cells expressing the intrinsically active p38 mutants. The continuous activities of the individual p38 induced feedback loops that inactivated the other p38s. Furthermore, a number of new phosphorylation sites on proteins relevant to stress responses and cancer, such as p53 and p27, were revealed in this study.  

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: Dganit Melamed Kadosh  

LAB HEAD: Arie Admon

PROVIDER: PXD038389 | Pride | 2023-10-24

REPOSITORIES: Pride