Cell Signaling

ProxHCR staining of E-cadherin/Beta-Catenin interactions in cells

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.

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

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