Cell Signaling
Description
In order for a cell to be able to react to signals in its environment, there are receptor proteins that, when activated, transmit signals into the cell that in many cases lead to changes in enzyme activity and/or gene expression patterns. This process is called signal transduction and affects cellular behaviors such as cell division, survival or movement, both under normal and pathological conditions. More specifically, we are interested in how receptors of the receptor tyrosine kinase type are activated and transmit signals into the cell. For many years, we have focused our work specifically on how PDGFR and EGFR (both belonging to the receptor tyrosine kinase family) can activate and terminate signal transduction in normal and cancer cells. To investigate signal transduction, we use chemical biology and various types of genetic manipulation of normal or cancer cells grown in the laboratory. Our long-term goal is to understand at a molecular level the processes of how PDGFR and EGFR signal, and be able to use this knowledge to identify therapeutic target proteins or processes, as well as identify diagnostic predictors.
Utvalda publikationer
Papadopoulos N, Lennartsson J and Heldin CH. PDGFRβ translocates to the nucleus and regulates chromatin remodeling via TATA element modifying factor 1.J Cell Biol. 2018 May 7;217(5):1701-1717
Heldin CH, Lennartsson J and Westermark B. Involvement of platelet-derived growth factor ligands and receptors in tumorigenesis. J Intern Med, 2018 283(1):16-44
Papadopoulos N and Lennartsson J. The PDGF/PDGFR pathway as a drug target.Mol Aspects Med, 2017 Nov 15, pii: S0098-2997(17)30140-1
Rorsman C, Tsioumpekou M, Heldin CH and Lennartsson J. The ubiquitin ligases c-Cbl and Cbl-b negatively regulate PDGF-BB-induced chemotaxis by affecting PDGFRb internalization and signaling. J Biol Chem 2016 May 27;291(22):11608-18
Tsioumpekou M, Papadopoulos N, Burovic F, Heldin CH and Lennartsson J. Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling. Cell Signal 2016 28:1422-1431
Sooman L, Ekman S, Tsakonas G, Alafuzoff I, Popova S, Jaiswal A, Navani S, Edqvist PE, Pontén F, Bergström S, Johansson M, Wu X, Blomquist E, Bergqvist M, Gullbo J and Lennartsson J. PTPN6 expression is epigenetically regulated and influences the response to therapy in high-grade gliomas. Tumor Biol, 2014 May;35(5):4479-88
Wu X, Sooman L, Wickström M, Fryknäs M, Dyrager C, Lennartsson J*, and Gullbo J* Alternative cytotoxic effects of the postulated IGF-1R inhibitor picropodophyllin (PPP) in vitro. Mol Cancer Ther, 2013 Aug;12(8):1526-36 *equally contributing and corresponding senior authors
Sooman L, Ekman S, Andersson C, Göransson-Kultima H, Isaksson A, Johansson F, Bergqvist M, Blomquist E, Lennartsson J and Gullbo J. Synergistic interactions between camptothecin and EGFR or RAC1 inhibitors and between imatinib and Notch signaling or RAC1 inhibitors in glioblastoma cell lines. Cancer Chemother Pharmacol, 2013 Aug;72(2):329-40
Lennartsson J, Ma H, Wardega P, Pelka K, Engström U, Hellberg C and Heldin CH. The Fer tyrosine kinase is important for platelet-derived growth factor-BB-induced Stat3 phosphorylation, colony formation is soft agar and tumor growth in vivo. J Biol Chem, 2013 May 31 288(22):15736-15744
Razmara M, Heldin CH and Lennartsson J. Platelet-derived growth factor-induced Akt phosphorylation requires mTOR/Rictor and phospholipase C-γ1, whereas S6 phosphorylation depends on mTOR/Raptor and phospholipase D. Cell Commun Signal, 2013 Jan 11;11(1):3
Publications
Part of Journal of Steroid Biochemistry and Molecular Biology, 2024
- DOI for Cellular responses to silencing of PDIA3 (protein disulphide-isomerase A3): Effects on proliferation, migration, and genes in control of active vitamin D
- Download full text (pdf) of Cellular responses to silencing of PDIA3 (protein disulphide-isomerase A3): Effects on proliferation, migration, and genes in control of active vitamin D
Depletion of the Rho GTPases Cdc42, Rac1 or RhoA reduces PDGF-induced STAT1 and STAT3 signaling
Part of Biochemistry and Biophysics Reports, 2024
Part of Biochemical and Biophysical Research Communications - BBRC, 2024
The E3 Ubiquitin Ligase TRIM21 Regulates Basal Levels of PDGFRβ
Part of International Journal of Molecular Sciences, 2023
SUMOylation of PDGF receptor α affects signaling via PLCγ and STAT3, and cell proliferation
Part of BMC Molecular and Cell Biology, 2023
Part of Biochemical and Biophysical Research Communications - BBRC, p. 195-201, 2023
- DOI for Activated EGFR and PDGFR internalize in separate vesicles and downstream AKT and ERK1/2 signaling are differentially impacted by cholesterol depletion
- Download full text (pdf) of Activated EGFR and PDGFR internalize in separate vesicles and downstream AKT and ERK1/2 signaling are differentially impacted by cholesterol depletion
Part of Biochemistry and Biophysics Reports, 2022
- DOI for Effects of 1a,25-dihydroxyvitamin D-3 and tacalcitol on cell signaling and anchorage-independent growth in T98G and U251 glioblastoma cells
- Download full text (pdf) of Effects of 1a,25-dihydroxyvitamin D-3 and tacalcitol on cell signaling and anchorage-independent growth in T98G and U251 glioblastoma cells
Part of Cellular and Molecular Life Sciences (CMLS), 2022
Part of Cellular Signalling, 2022
- DOI for Differential impact of lipid raft depletion on platelet-derived growth factor (PDGF)-induced ERK1/2 MAP-kinase, SRC and AKT signaling
- Download full text (pdf) of Differential impact of lipid raft depletion on platelet-derived growth factor (PDGF)-induced ERK1/2 MAP-kinase, SRC and AKT signaling
Structure-based discovery of novel small molecule inhibitors of platelet-derived growth factor-B
Part of Bioorganic chemistry (Print), 2020
Part of Theranostics, p. 1122-1135, 2020
Part of Biochemical and Biophysical Research Communications - BBRC, p. 469-474, 2019
Dynamin inhibitors impair platelet-derived growth factor beta-receptor dimerization and signaling
Part of Experimental Cell Research, p. 69-79, 2019
Part of Journal of Cell Biology, p. 1701-1717, 2018
PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway
Part of Scientific Reports, 2017
Part of Journal of Biological Chemistry, p. 11608-11618, 2016
Part of Cellular Signalling, p. 1422-1431, 2016
Part of International Journal of Molecular Medicine, 2015
FGF2 as a potential prognostic biomarker for proneural glioma patients
Part of Acta Oncologica, p. 385-394, 2015
Part of PLOS ONE, 2015
Part of Cellular Signalling, p. 2209-2219, 2015
Picropodophyllin inhibits proliferation and survival of diffuse large B-cell lymphoma cells
Part of Medical Oncology, 2015
NR4A1 Promotes PDGF-BB-Induced Cell Colony Formation in Soft Agar
Part of PLOS ONE, 2014
Part of Tumor Biology, p. 4479-4488, 2014
Alternative Cytotoxic Effects of the Postulated IGF-IR Inhibitor Picropodophyllin In Vitro
Part of Molecular Cancer Therapeutics, p. 1526-1536, 2013
Part of Journal of Biological Chemistry, p. 15736-15744, 2013
Part of Traffic, p. 1242-1254, 2013
Vandetanib combined with a p38 MAPK inhibitor synergistically reduces glioblastoma cell survival
Part of Medical Oncology, p. 638, 2013
Part of International Journal of Oncology, p. 297-304, 2013
Part of Cancer Chemotherapy and Pharmacology, p. 329-340, 2013
Part of Cell Communication and Signaling, 2013
Part of Cold Spring Harbor Perspectives in Biology, 2013
Part of Neuro-Oncology, 2012
MKP3 negatively modulates PDGF-induced Akt and Erk5 phosphorylation as well as chemotaxis
Part of Cellular Signalling, p. 635-640, 2012
Part of International Journal of Oncology, p. 176-184, 2012
The HER2-binding Affibody Molecule (ZHER2:342)2 Increases Radiosensitivity in SKBR-3 cells
Part of PLOS ONE, 2012
Part of European Journal of Cancer, 2012
Part of Acta Oncologica, p. 69-76, 2012
Part of Cell Communication and Signaling, p. 19, 2012
Part of Cellular Signalling, p. 1050-1056, 2011
Part of Cellular Signalling, p. 280-287, 2011
SOX10 expression in superficial spreading and nodular malignant melanomas
Part of Melanoma research, p. 468-478, 2010
Part of Proceedings of the National Academy of Sciences of the United States of America, p. 12216-12221, 2010
Part of Journal of Experimental Medicine, p. 867-880, 2010
Mutation of tyrosine residue 857 in the PDGF β-receptor affects cell proliferation but not migration
Part of Cellular Signalling, p. 1363-1368, 2010
Erk 5 is necessary for sustained PDGF-induced Akt phosphorylation and inhibition of apoptosis
Part of Cellular Signalling, p. 955-960, 2010
Effects of an EGFR-binding affibody molecule on intracellular signaling pathways
Part of International Journal of Oncology, p. 967-972, 2010
Part of Journal of Biological Chemistry, p. 4626-4634, 2009
Part of Journal of Biological Chemistry, p. 33456-33465, 2009
Part of Arthritis and Rheumatism, p. 1137-1144, 2009