A5024529237- Protein Kinase Regulation and GTPase Signaling
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Hippo pathway signaling and YAP/TAZ
- Mitochondrial Function and Pathology
- Fungal and yeast genetics research
- Wnt/β-catenin signaling in development and cancer
- Cardiomyopathy and Myosin Studies
- Ubiquitin and proteasome pathways
- TGF-β signaling in diseases
- RNA Research and Splicing
- Melanoma and MAPK Pathways
- ATP Synthase and ATPases Research
- Protein Tyrosine Phosphatases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Retinal Development and Disorders
- Occupational and environmental lung diseases
- 3D Printing in Biomedical Research
- Force Microscopy Techniques and Applications
- PI3K/AKT/mTOR signaling in cancer
- Muscle Physiology and Disorders
- Cancer-related Molecular Pathways
- Gut microbiota and health
Uppsala University
2007-2024
Karolinska Institutet
2011-2023
Science for Life Laboratory
2021
Ludwig Cancer Research
2000-2009
Ludwig Cancer Research
1997-2008
Massachusetts General Hospital
2001
Stockholm University
1989-1996
Energy use, mainly to reverse ion movements in neurons, is a fundamental constraint on brain information processing. Trafficking of mitochondria locations neurons where there are large fluxes essential for powering neural function. Mitochondrial trafficking regulated by Ca2+ entry through ionotropic glutamate receptors, but the underlying mechanism unknown. We show that protein Miro1 links KIF5 motor proteins, allowing move along microtubules. This linkage inhibited micromolar levels binding...
Rac and Cdc42 regulate a variety of responses in mammalian cells including formation lamellipodia filopodia, activation the JNK MAP kinase cascade, induction G1 cell cycle progression. is also one downstream targets required for Ras- induced malignant transformation. containing Y40C effector site substitution no longer intact with Ser/Thr p65PAK are unable to activate pathway. However, they still induce cytoskeletal changes an F37A substitution, on other hand, interacts p160ROCK or We...
Calcium oscillations suppress mitochondrial movements along the microtubules to support on-demand distribution of mitochondria. To activate this mechanism, Ca(2+) targets a yet unidentified cytoplasmic factor that does not seem be microtubular motor or kinase/phosphatase. Here, we have studied dependence dynamics on Miro GTPases reside in mitochondria and contain two EF-hand Ca(2+)-binding domains, H9c2 cells primary neurons. At resting [Ca(2+)] ([Ca(2+)](c)), were enhanced by overexpression...
The Rho GTPases are related to the Ras proto-oncogenes and consist of 22 family members. These proteins have important roles in regulating organization actin filament system, thereby morphogenesis vertebrate cells as well their ability migrate. In an effort compare effects all members GTPase family, active were transfected into porcine aortic endothelial on system monitored. Cdc42, TCL (TC10-like), Rac1–Rac3 RhoG induced formation lamellipodia, whereas Rac1 Rac2 also thick bundles filaments....
Transforming growth factor-beta (TGF-beta) is a potent regulator of cell and differentiation in many types. The Smad signaling pathway constitutes main signal transduction route downstream TGF-beta receptors. We studied TGF-beta-induced rearrangements the actin filament system found that 1 treatment PC-3U human prostate carcinoma cells resulted rapid formation lamellipodia. Interestingly, this response was shown to be independent pathway; instead, it required activity Rho GTPases Cdc42 RhoA,...
The human genomic sequencing effort has revealed the presence of a large number Rho GTPases encoded by genome. Here we report characterization new family with atypical features. These proteins, which were called Miro-1 and Miro-2 (for mitochondrialRho), have tandem GTP-binding domains separated linker region containing putative calcium-binding EF hand motifs. Genes encoding Miro-like proteins found in several eukaryotic organisms from <i>Saccharomyces cerevisiae</i>,<i>Caenorhabditis...
The inhibitory Smad7, a direct target gene for transforming growth factor-β (TGF-β), mediates TGF-β1–induced apoptosis in several cell types. Herein, we report that of human prostate cancer PC-3U cells induced by TGF-β1 or Smad7 overexpression is caused specific activation the p38 mitogen-activated protein kinase pathway TGF-β–activated 1 (TAK1)- and 3 (MKK3)-dependent manner. Expression dominant negative p38, MKK3, incubation with selective inhibitor...
The development of the embryonic vascular system into a highly ordered network requires precise control over migration and branching endothelial cells (ECs). We have previously identified angiomotin (Amot) as receptor for angiogenesis inhibitor angiostatin. Furthermore, DNA vaccination targeting Amot inhibits tumor growth. However, little is known regarding role in physiological angiogenesis. therefore investigated neovascularization during zebrafish mouse embryogenesis. Here we report that...
Estrogen supports urothelial defense against infection by increasing the expression of antimicrobial peptides and protecting epithelial integrity.
Oncogenes deregulate fundamental cellular functions, which can lead to development of tumors, tumor-cell invasion, and metastasis. As the mechanical properties cells govern cell motility, we hypothesized that oncogenes promote invasion by inducing cytoskeletal changes increase stiffness. We show simian virus 40 large T antigen, c-Myc, cyclin E induce spatial reorganization vimentin intermediate filament network in cells. At level, this manifests as increased width fibers collapse network....
Abstract Although chromosome partitioning during mitosis is well studied, the molecular mechanisms that allow proper segregation of cytoplasmic organelles in human cells are poorly understood. Here we show mitochondria interact with growing microtubule tips and transported towards daughter cell periphery at end mitosis. This phenomenon promoted by direct cycle-dependent interaction mitochondrial protein Miro cytoskeletal-associated Cenp-F. Cenp-F recruited to time cytokinesis associates...
RHO GTPase-activating proteins (RHOGAPs) are one of the major classes regulators RHO-related protein family that crucial in many cellular processes, motility, contractility, growth, differentiation, and development. Using database searches, we extracted 66 distinct human RHOGAPs, from which 57 have a common catalytic domain capable terminating signaling by stimulating slow intrinsic GTP hydrolysis (GTPase) reaction. The specificity majority members RHOGAP is largely uncharacterized. Here,...
ABSTRACT A mammalian homologue of the PDZ domain containing Caenorhabditis elegans protein PAR-6 was found in a yeast two-hybrid system screen as binding to Rho family member Cdc42. contains and C. it has been shown be crucial for asymmetric cleavage establishment cell polarity during first divisions growing embryo. Mammalian interacted with Cdc42 Rac1 both vitro assays. Co-immunoprecipitation experiments, employing transiently transfected Cos-1 cells, further confirmed that are...
PTPL1 is an intracellular protein-tyrosine phosphatase that contains five PDZ domains. Here, we present the cloning of a novel 150-kDa protein, four most C-terminal amino acid residues which specifically interact with fourth domain PTPL1. The molecule GTPase-activating protein (GAP) domain, cysteine-rich, putative Zn2+- and diacylglycerol-binding region sequence homology to product Caenorhabditis elegans geneZK669.1a. GAP active on Rho, Rac, Cdc42in vitro but clear preference for Rho; refer...
Members of the transforming growth factor β (TGF-β) and Wnt/wingless superfamilies regulate cell fate during development tissue maintenance. Here we report that Smad7 interacts with β-catenin lymphoid enhancer binding 1/T-cell-specific (LEF1/TCF), transcriptional regulators in Wnt signaling, a TGF-β-dependent manner. was found to be required for TGF-β1-induced accumulation LEF1 human prostate cancer (PC-3U) cells as well keratinocytes (HaCaT cells). Moreover, when endogenous repressed by...
Protein tyrosine phosphatases (PTPs) are regulated through reversible oxidation of the active-site cysteine. Previous studies have implied soluble reactive oxygen species (ROS), like H 2 O , as mediators PTP oxidation. The potential role(s) peroxidized lipids in not been described. This study demonstrates that increases cellular lipid peroxides, induced by disruption glutathione peroxidase 4, induce and reduce activity PDGF receptor targeting PTPs. These effects were accompanied...
Abstract Diabetes is known to increase susceptibility infections, partly due impaired granulocyte function and changes in the innate immunity. Here, we investigate effect of diabetes, high glucose on expression antimicrobial peptide, psoriasin putative consequences for E. coli urinary tract infection. Blood, urine, urine exfoliated cells from patients are studied. The influence insulin examined during hyperglycemic clamps individuals with prediabetes euglycemic hyperinsulinemic clamped type...