A5034562303- Cytokine Signaling Pathways and Interactions
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Immune Cell Function and Interaction
- interferon and immune responses
- Pharmacological Effects of Natural Compounds
- Protein Kinase Regulation and GTPase Signaling
- NF-κB Signaling Pathways
- T-cell and B-cell Immunology
- Kruppel-like factors research
- Rheumatoid Arthritis Research and Therapies
- Protein Tyrosine Phosphatases
- Chronic Myeloid Leukemia Treatments
- PI3K/AKT/mTOR signaling in cancer
- RNA Research and Splicing
- Immune Response and Inflammation
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Ubiquitin and proteasome pathways
- Chronic Lymphocytic Leukemia Research
- Peptidase Inhibition and Analysis
- HER2/EGFR in Cancer Research
- Mechanisms of cancer metastasis
- Neurobiology and Insect Physiology Research
University of Helsinki
2003-2025
Tampere University
2016-2025
Fimlab (Finland)
2018-2025
Tampere University Hospital
2013-2024
Pirkanmaa Hospital District
2018-2023
Osaka Medical and Pharmaceutical University
2021
Tampere University of Applied Sciences
2000-2013
FIT Biotech (Finland)
2012
Institute of Biomedical Science
2011
University of Southern Denmark
2007
A recently defined family of cytokines, consisting ciliary neurotrophic factor (CNTF), leukemia inhibitory (LIF), oncostatin M (OSM), and interleukin-6 (IL-6), utilize the Jak-Tyk cytoplasmic tyrosine kinases. The β receptor components for this cytokine family, gp130 LIF β, constitutively associate with Activation these kinases occurs as a result ligand-induced dimerization components. Unlike other receptors studied to date, CNTF all known members but induce distinct patterns phosphorylation...
Interleukin-2 (IL-2) signaling requires the dimerization of IL-2 receptor β (IL-2Rβ) and common γ (γ c ) chains. Mutations can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain ), IL-9 is shown here induced tyrosine phosphorylation activation Janus family kinases Jak1 Jak3. Jak3 associated with IL-2Rβ , respectively; Jak3-IL-2Rβ increased Jak3-γ associations. Truncations a point mutation causing moderate (XCID), decreased...
The interleukin-2 receptor (IL-2R) consists of three subunits: the IL-2Rα, IL-2Rβ, and IL-2Rγ chains, last which is also used in receptors for IL-4, IL-7, IL-9. Stimulation with IL-2 induces tyrosine phosphorylation activation Janus kinases Jak1 Jak3. Jak3 were found to be selectively associated "serine-rich" region IL-2Rβ carboxyl-terminal IL-2Rγ, respectively. Both regions necessary signaling. Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive after...
Interleukin 3 (IL-3) regulates the proliferation and differentiation of hematopoietic cells. Although IL-3 receptor chains lack kinase catalytic domains, induces tyrosine phosphorylation cellular proteins. To investigate potential role JAK family protein-tyrosine kinases in signal transduction, we have obtained full-length cDNA clones for murine Jak1 Jak2 prepared antiserum against predicted Using antisera Jak2, demonstrate that stimulation results rapid specific activates its vitro activity.
Long QT syndrome (LQTS) is caused by functional alterations in cardiac ion channels and associated with prolonged repolarization time increased risk of ventricular arrhythmias. Inherited type 2 LQTS (LQT2) drug-induced both result from altered function the hERG channel. We investigated whether electrophysiological characteristics LQT2 can be recapitulated vitro using induced pluripotent stem cell (iPSC) technology. Spontaneously beating cardiomyocytes were differentiated two iPSC lines...
Protein kinase-like domains that lack conserved residues known to catalyse phosphoryl transfer, termed pseudokinases, have emerged as important signalling across all kingdoms of life. Although predicted function principally catalysis-independent protein-interaction modules, several pseudokinase been attributed unexpected catalytic functions, often amid controversy. We established a thermal-shift assay benchmark technique define the nucleotide-binding properties domains. Unlike in vitro...
Activation of Jak tyrosine kinases through hematopoietic cytokine receptors occurs as a consequence ligand-induced aggregation receptor-associated Jaks and their subsequent autophosphorylation. consist C-terminal kinase domain, pseudokinase domain unknown function, homology (JH) domains 3 to 7, implicated in receptor-Jak interaction. We analyzed the functional roles different protein activation Jak2. Deletion analysis Jak2 showed that but not JH 7 negatively regulated catalytic activity well...
Interferons induce transcriptional activation through tyrosine phosphorylation of the latent, cytoplasmic transcription factor interferon-stimulated gene factor-3 (ISGF-3). Growth factors and cytokines were found to use a similar pathway: The 91-kilodalton subunit ISGF-3 was activated phosphorylated in response epidermal growth (EGF), platelet-derived factor, colony stimulating factor-1. acquired DNA binding activity accumulated nuclei. Activation required major sites for autophosphorylation...
Janus (Jak) tyrosine kinases contain a kinase (JH1) domain adjacent to catalytically inactive pseudokinase (JH2). The JH2 has been implicated in regulation of Jak activity, but its function remains poorly understood. Here, we found that the negatively regulates activity Jak2 and Jak3. Deletion resulted increased phosphorylation Jak2- Jak3-JH2 deletion mutants as well coexpressed STAT5. In cytokine receptor signaling, domains interferon-gamma interleukin-2-independent STAT activation,...
The interleukin 6 receptor-associated signal transducer, gp130, is shared by receptor complexes for leukemia inhibitory factor, oncostatin M, ciliary neurotrophic and 11. We show here that JAK2 kinase rapidly tyrosine phosphorylated in mouse embryonic stem cells whose pluripotentiality maintained only gp130-sharing cytokines after stimulation known to induce gp130 homodimerization. JAK1 also phosphorylated, but a lesser extent, under the same conditions. Comparable results are obtained with...
The family of cytoplasmic Janus (Jak) tyrosine kinases plays an essential role in cytokine signal transduction, regulating cell survival and gene expression.Ligand-induced receptor dimerization results phosphorylation Jak2 on activation loop Y1007 stimulation its catalytic activity, which, turn, several downstream signaling cascades.Recently, the activity has been found to be subject negative regulation through various mechanisms including association with SOCS proteins.Here we show that...