A5063451537- Neuroscience and Neuropharmacology Research
- Melanoma and MAPK Pathways
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Neurogenesis and neuroplasticity mechanisms
- Signaling Pathways in Disease
- Cell death mechanisms and regulation
- Cellular Mechanics and Interactions
- Receptor Mechanisms and Signaling
- Nerve injury and regeneration
- Ion channel regulation and function
- Cell Adhesion Molecules Research
- Genetics and Neurodevelopmental Disorders
- Protein Kinase Regulation and GTPase Signaling
- Metabolomics and Mass Spectrometry Studies
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Proteomics Techniques and Applications
- Cancer-related Molecular Pathways
- Zebrafish Biomedical Research Applications
- Nuclear Receptors and Signaling
- Hereditary Neurological Disorders
- Phosphodiesterase function and regulation
- Autophagy in Disease and Therapy
- RNA regulation and disease
Åbo Akademi University
2014-2025
University of Turku
2013-2024
Turku Centre for Computer Science
2020-2024
Turku Centre for Biotechnology
2009-2021
University of Dundee
1993-1994
The Royal Free Hospital
1993
University of London
1993
University College London
1993
c-Jun is considered a major regulator of both neuronal death and regeneration. Stress in primary cultured CNS neurons induces phosphorylation serines 63 73 increased protein. However, total N-terminal protein kinase (JNK) activity does not increase, no satisfactory explanation for this paradox has been available. Here we demonstrate that stress strong activation JNK2/3 the presence constitutively highly active JNK1. Correspondingly, from JNK1<sup>−/−</sup>mice show lower constitutive...
c-Jun NH2-terminal kinases (JNKs) are essential during brain development, when they regulate morphogenic changes involving cell movement and migration. In the adult, JNK determines neuronal cytoarchitecture. To help uncover molecular effectors for JNKs in these events, we affinity purified JNK-interacting proteins from brain. This revealed that stathmin family microtubule-destabilizing SCG10, SCLIP, RB3, RB3′ interact tightly with JNK. Furthermore, SCG10 is also phosphorylated by vivo on...
Normal functioning of the nervous system requires precise regulation dendritic shape and synaptic connectivity. Here, we report a severe impairment structures in cerebellum motor cortex c-Jun N-terminal kinase 1 (JNK1)-deficient mice. Using an unbiased screen for candidate mediators, identify dendrite-specific high-molecular-weight microtubule-associated protein 2 (MAP2) as JNK substrate brain. We subsequently show that MAP2 is phosphorylated by intact cells proline-rich domain...
c-Jun N-terminal kinases (JNKs) typically respond strongly to stress, are implicated in brain development, and believed mediate neuronal apoptosis. Surprisingly, however, JNK does not characteristically stress cultured cerebellar granule (CBG) neurons, a widely exploited CNS model for studies of death despite the regulation its substrate c-Jun. To understand this anomaly, we characterized CBG neurons. We find that specific activity is elevated considerably above from neuron-like cell lines...
Lithium has been used as an effective mood-stabilizing drug for the treatment of manic episodes and depression 50 years. More recently, lithium found to protect neurons from death induced by a wide array neurotoxic insults. However, molecular basis prophylactic effects have remained obscure. A target lithium, glycogen synthase kinase 3 (GSK-3), is implicated in neuronal after trophic deprivation. The mechanism whereby GSK-3 exerts its also unknown. Here we show that blocks canonical c-Jun...
Loss-of-function mutations in the IKBKAP gene, which encodes IKAP (ELP1), cause familial dysautonomia (FD), with defective neuronal development and maintenance. Molecular mechanisms leading to FD are poorly understood. We demonstrate that various RNA-interference-based depletions of lead adhesion migration several cell types, including rat primary neurons. The defects could be rescued by reintroduction wild-type but not FD-IKAP, a truncated form constructed according mutation found majority...
Integrin trafficking from and to the plasma membrane controls many aspects of cell behavior including motility, invasion, cytokinesis. Recruitment integrin cargo endocytic machinery is regulated by small GTPase Rab21, but detailed molecular mechanisms underlying recruitment are yet unknown. Here we identify an important role for p120RasGAP (RASA1) in recycling endocytosed α/β1-integrin heterodimers membrane. Silencing attenuated augmented motility. Mechanistically, interacted with...
Cell migration is a fundamental biological function, critical during development and regeneration, whereas deregulated underlies neurological birth defects cancer metastasis. MARCKS-like protein 1 (MARCKSL1) widely expressed in nervous tissue, where, like Jun N-terminal kinase (JNK), it required for neural tube formation, though the mechanism unknown. Here we show that MARCKSL1 directly phosphorylated by JNK on C-terminal residues (S120, T148, T183). This phosphorylation enables to bundle...
Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown hypothesis itself controversial. Here we show mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased in hippocampus characterized by enhanced cell proliferation survival, maturation ventral region. Correspondingly, anxiety behaviour reduced a battery of tests, except when...
Cerebellar granule neurons cultured with serum develop a mature neuronal phenotype, including stimulus-coupled release of glutamate, and depend on elevated potassium for survival. We find that cells undergo two phases cell death. By 6 d in vitro , 30–50% the present are dead; after this time remaining die. Elevated prevents only later phase death, whereas neurotrophins protect these against early Factors bind p75 NTR or TNF-R, members same receptor family, exhibit voltage-sensitive calcium...
Abstract Jurkat T cells undergo rapid apoptosis upon stimulation of the Fas/APO-1 (CD95) receptor. We examined role mitogen-activated protein kinase (MAPK) cascade as a negative regulator Fas-mediated apoptosis. To this end, we used both physiologic and artificial activators MAPK, all which activate MAPK by distinct routes. activity could be efficiently elevated two cell mitogens, lectin PHA an agonistic Ab to receptor complex well type 1 2A phosphatase inhibitor, calyculin A, C-activating...
The role of protein kinase C (PKC) in the regulation transmitter glutamate release from rat cerebral cortical synaptosomes is investigated.Two depolarization protocols are used: first, elevated KCl, which produces a clamped depolarization, and second, 4-aminopyridine, evokes spontaneous "action potentials" allowing any potential modulation Na+ or K+ channels to influence release.Although PKC inhibitor Ro 31-8220 prevents both depolarization-evoked phorbol dibutyrate (PDBu)-evoked...
JNKs are implicated in a range of brain pathologies and receive considerable attention as potential therapeutic targets. However, also regulate physiological homeostatic processes. An attractive hypothesis from the drug development perspective is that distinct JNK isoforms mediate "physiological" "pathological" responses. this lacks experimental evaluation. Here we investigate isoforms, subcellular pools, c-Jun/ATF2 targets death central nervous system neurons following withdrawal trophic...
Neuronal outgrowth occurs via coordinated remodeling of the cytoskeleton involving both actin and microtubules. Microtubule stabilization drives extending neurite, yet little is known molecular mechanisms whereby extracellular cues regulate microtubule dynamics. Bone morphogenetic proteins (BMPs) play an important role in neuronal differentiation morphogenesis, BMP7 particular induces formation dendrites. Here, we show that microtubules a MAP2-dependent cell culture model dendrites primary...
4-Aminopyridine evokes repetitive firing of synaptosomes and exocytosis glutamate by inhibiting a dendrotoxin-sensitive K+ channel responsible for stabilizing the membrane potential. We have shown previously that activation protein kinase C (PKC) high concentrations phorbol ester (4 beta-phorbol dibutyrate) can increase release dendrotoxin-insensitive ion channel, whereas metabotropic receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate [(1S,3R)-ACPD] mimics action 4...
Abstract Background Vibrio parahaemolyticus is a food-borne pathogen causing inflammation of the gastrointestinal epithelium. Pathogenic strains this bacterium possess two Type III Secretion Systems (TTSS) that deliver effector proteins into host cells. In order to better understand human cell responses V. , modulation Mitogen Activated Protein Kinase (MAPK) activation in epithelial cells by an O3:K6 clinical isolate, RIMD2210633, was investigated. The importance MAPK for ability be...
Abstract Deficits in protein synthesis are associated with Parkinson’s disease (PD). However, it is not known which proteins affected or if there differences between patients sporadic and Leucine-Rich Repeat Kinase 2 (LRRK2) G2019S PD, the most common monogenic form. Here we used bio-orthogonal non-canonical amino acid tagging for global analysis of newly translated fibroblasts from LRKK2-G2019S patients. Quantitative proteomic revealed that several nascent were reduced PD samples compared...