title: Reactive oxygen species exert opposite effects on Tyr23 phosphorylation of the nuclear and cortical pools of annexin A2.
abstract: Annexin A2 (AnxA2) is a multi-functional and -compartmental protein whose subcellular localisation and functions are tightly regulated by its post-translational modifications. AnxA2 and its Tyr23-phosphorylated form (pTyr23AnxA2) are involved in malignant cell transformation, metastasis and angiogenesis. Here, we show that H2O2 exerts rapid, simultaneous and opposite effects on the Tyr23 phosphorylation status of AnxA2 in two distinct compartments of rat pheochromocytoma (PC12) cells. Reactive oxygen species induce dephosphorylation of pTyr23AnxA2 located in the PML bodies of the nucleus, whereas AnxA2 associated with F-actin at the cell cortex is Tyr23 phosphorylated. The H2O2-induced responses in both compartments are transient and the pTyr23AnxA2 accumulating at the cell cortex is subsequently incorporated into vesicles and then released to the extracellular space. Blocking nuclear export by leptomycin B does not affect the nuclear pool of pTyr23AnxA2, but increases the amount of total AnxA2 in this compartment, indicating that the protein might have several functions in the nucleus. These results suggest that Tyr23 phosphorylation can regulate the function of AnxA2 at distinct subcellular sites.
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen N-5009, Norway Molecular Imaging Center (MIC), University of Bergen, Jonas Lies vei 91, Bergen N-5009, Norway.
authors.forename: Ann Kari
authors.initials: AK
authors.lastname: Grindheim
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen N-5009, Norway.
authors.forename: Hanne
authors.initials: H
authors.lastname: Hollås
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen N-5009, Norway.
authors.forename: Aase M
authors.initials: AM
authors.lastname: Raddum
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen N-5009, Norway Molecular Imaging Center (MIC), University of Bergen, Jonas Lies vei 91, Bergen N-5009, Norway.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Saraste
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen N-5009, Norway Anni.Vedeler@biomed.uib.no.
authors.forename: Anni
authors.initials: A
authors.lastname: Vedeler
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D002462:Cell Membrane; D002467:Cell Nucleus / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress; D016716:PC12 Cells; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000199:Actins; D017306:Annexin A2; D017382:Reactive Oxygen Species; D014443:Tyrosine; D006861:Hydrogen Peroxide
keywords: Annexin A2; Cell cortex; Nucleus; Oxidative stress; Tyrosine phosphorylation