A. Wiedlocha

Altered cell signaling in growth regulation is a prerequisite for cancer development. Our group studies fibroblast growth factor (FGF) signaling mechanisms and the translocation of FGF1 and FGF2 into cells. We found that, in addition to the well known mechanism of signaling through the tyrosine kinase receptor, FGF1 similarly to FGF2 is able to translocate into cells to fulfill the signal. We are going to understand in details mechanisms of FGF action including (i) activation of signaling network, internalization and down-regulation of activated FGF receptors. (ii) FGF1 and FGF2 translocation into the cytosol and nucleus, (iii) identification of new intracellular FGF1 and FGF2 binding partners. New findings in this field would be beneficial for finding new molecular targets for anti-cancer therapy.

Antoni Wiedlocha's Group click to enlarge image

Contact information:
Email: Antoni.Wiedlocha@rr-research.no
Department of Biochemistry, Institute for Cancer Research
The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway
Phone +47 22 78 19 30 (Wiedlocha), Switchboard: +47 22 93 40 00

Wiedlocha A, Nilsen T, Wesche J, Sørensen V, Malecki J, Marcinkowska E, Olsnes S (2005)
Phosphorylation-regulated nucleocytoplasmic trafficking of internalized fibroblast growth factor-1
Mol Biol Cell, 16 (2), 794-810
PubMed 15574884

Wesche J, Malecki J, Wiedlocha A, Skjerpen CS, Claus P, Olsnes S (2006)
FGF-1 and FGF-2 require the cytosolic chaperone Hsp90 for translocation into the cytosol and the cell nucleus
J Biol Chem, 281 (16), 11405-12
PubMed 16495214

Nilsen T, Rosendal KR, Sørensen V, Wesche J, Olsnes S, Wiedlocha A (2007)
A nuclear export sequence located on a beta-strand in fibroblast growth factor-1
J Biol Chem, 282 (36), 26245-56
PubMed 17616529

Zhen Y, Sørensen V, Jin Y, Suo Z, Wiedlocha A (2007)
Indirubin-3'-monoxime inhibits autophosphorylation of FGFR1 and stimulates ERK1/2 activity via p38 MAPK
Oncogene, 26 (44), 6372-85
PubMed 17533378

Sørensen V, Zhen Y, Zakrzewska M, Haugsten EM, Wälchli S, Nilsen T, Olsnes S, Wiedlocha A (2008)
Phosphorylation of fibroblast growth factor (FGF) receptor 1 at Ser777 by p38 mitogen-activated protein kinase regulates translocation of exogenous FGF1 to the cytosol and nucleus.
Mol Cell Biol. 12, 4129-41
PubMed 18411303