Research Theme within School of Biosciences: Molecular and Cell Biology
Receptor tyrosine kinase activation regulates a wide variety of cellular responses, including cell migration, survival and proliferation. To elicit an appropriate type response to extracellular factors, it is important that the level of receptor activation is tightly regulated. Our studies are focused on understanding how signals initiated by platelet-derived growth factor (PDGF)-receptors are modified to fine-tune the cellular response to its microenvironment. PDGFs are potent stimulators of cell growth, survival and motility, and increased PDGF receptor signalling is associated with various diseases including atherosclerosis, restenosis, various fibrotic diseases and cancer.
Specifically, we are
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identifying protein tyrosine phosphatases that modify PDGF receptor signalling
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exploring the role of endocytosis and intracellular receptor sorting in signal transduction
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investigating how oncogenic Ras regulates PDGF receptor sorting and signalling
Selected publications:
The LAR protein tyrosine phosphatase enables PDGF β-receptor activation through attenuation of the c-Abl kinase activity. W. Zheng, J. Lennartsson, W. Hendriks C.-H. Heldin, and C. Hellberg
Cell. Signalling 23:1050–1056, 2011
Combination therapy using imatinib and vatalanib improves the therapeutic efficiency of paclitaxel towards a mouse melanoma tumor.
A. Klosowska Wardenga, Y. Hasumi, A. Åhgren, C.-H. Heldin and C. Hellberg.
Melanoma Research. 21(1):57-65, February 2011.
doi: 10.1097/CMR.0b013e32833faf4d
Critical role of the platelet-derived growth factor receptor (PDGFR)-β transmembrane domain in the TEL-PDGFRβ cytosolic oncoprotein. F. Toffalini, C. Hellberg and J.-B. Demoulin. J. Biol. Chem.285: 12268-12278, 2010
Activation of protein kinase Ca is necessary for sorting the PDGF β-receptor to Rab4a-dependent recycling. C. Hellberg, C. Schmees, S. Karlsson, A. Åhgren and C.-H. Heldin
Mol. Biol. Cell 2009 Jun;20(12):2856-63.
Identification of a subset of pericytes that are responding to combination therapy targeting PDGF and VEGF signaling
Y. Hasumi, A. Klosowska-Wardega, M. Furuhashi, A. Östman, C.-H. Heldin, C. Hellberg
Int J Cancer 2007 Dec 15;121(12):2606-14.
Dynamic changes in the expression of DEP-1 and other PDGF receptor-antagonizing PTPs during onset and termination of neointima formation.
K. Kappert, J. Paulsson, J. Sparwel, Leppänen O, C. Hellberg, A. Östman, P. Micke
FASEB J. 2007 Feb;21(2):523-34 .
Protein tyrosine phosphatases and cancer
A. Östman, C. Hellberg and F.D. Böhmer
Nature Rev. Cancer 6: 307-320 2006
Loss of T-cell protein tyrosine phosphatase induces recycling of the platelet-derived growth factor (PDGF) β-receptor but not the PDGF α-receptor.
S. Karlsson, K. Kowanetz, Å. Sandin, C. Persson, C.-H. Heldin, A. Östman and C. Hellberg.
Molecular Biology of the Cell 17: 4846-4855, 2006.
Site-selective regulation of PDGF β-receptor tyrosine phosphorylation by TC-PTP.
C. Persson, C. Sävenhed, A. Bourdeau, M.L. Tremblay, B. Markova, F.D. Böhmer, F.G. Haj, B.G. Neel, A. Elson, C.-H. Heldin, L. Rönnstrand, A. Östman and C. Hellberg
Mol. Cell Biol. 24(5): 2190-2201, 2004.