Jacek Otlewski
University of Wrocław
Binding siteBiophysicsMutantMolecular biologyCytotoxic T cellReceptorEnzymeChemistryPhage displayTrypsin inhibitorChymotrypsinTrypsinProtein structureBiochemistryStereochemistryFibroblast growth factorCrystallographyFibroblast growth factor receptorBiologyCell biologyCancer cell
153Publications
44H-index
4,499Citations
Publications 152
Newest
#1Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
#2Martyna Sochacka (UWr: University of Wrocław)H-Index: 2
Last. Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
view all 7 authors...
Fibroblast growth factor 1 (FGF1) has been shown to interact with integrin αvβ3 through a specific binding site, involving Arg35 residue. The FGF1 mutant (R35E) with impaired integrin binding was found to be defective in its proliferative response, although it was still able to interact with FGF receptors (FGFR) and heparin and induce the activation of downstream signaling pathways. Here, we demonstrate that the lack of mitogenic potential of R35E mutant is directly caused by its decreased therm...
3 CitationsSource
The targeted therapies are rapidly evolving modalities of cancer treatment. The largest group of currently developed biopharmaceuticals are antibody-drug conjugates (ADCs). Here, we developed a new modular strategy for the generation of cytotoxic bioconjugates, containing a homodimer of targeting protein and two highly-potent anticancer drugs with distinct mechanisms of action. Instead of antibody, we applied human fibroblast growth factor 2 (FGF2) as a targeting protein. We produced a conjugate...
4 CitationsSource
#1Marika Kucińska (UWr: University of Wrocław)H-Index: 4
#2Natalia Porębska (UWr: University of Wrocław)H-Index: 3
Last. Łukasz Opaliński (UWr: University of Wrocław)H-Index: 7
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Fibroblast growth factor receptors (FGFRs) are integral membrane proteins that transmit signals through the plasma membrane. FGFRs signaling needs to be precisely adjusted as aberrant FGFRs function is associated with development of human cancers or severe metabolic diseases. The subcellular localization, trafficking and function of FGFRs rely on the formation of multiprotein complexes. In this study we revealed galectins, lectin family members implicated in cancer development and progression, a...
6 CitationsSource
#1Marta Latko (UWr: University of Wrocław)H-Index: 3
#2Aleksandra Czyrek (UWr: University of Wrocław)H-Index: 6
Last. Łukasz Opaliński (UWr: University of Wrocław)H-Index: 7
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Fibroblast growth factors (FGFs) and their receptors (FGFRs) constitute signaling circuits that transmit signals across the plasma membrane, regulating pivotal cellular processes like differentiation, migration, proliferation, and apoptosis. The malfunction of FGFs/FGFRs signaling axis is observed in numerous developmental and metabolic disorders, and in various tumors. The large diversity of FGFs/FGFRs functions is attributed to a great complexity in the regulation of FGFs/FGFRs-dependent signa...
22 CitationsSource
#1Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
#2Lukasz Opalinski (UWr: University of Wrocław)H-Index: 3
Last. Antoni G Wiedlocha (University of Oslo)H-Index: 23
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Mitogen-activated protein kinases (MAPK): Erk1 and Erk2 are key players in negative-feedback regulation of fibroblast growth factor (FGF) signaling. Upon activation, Erk1 and Erk2 directly phosphorylate FGF receptor 1 (FGFR1) at a specific serine residue in the C-terminal part of the receptor, substantially reducing the tyrosine phosphorylation in the receptor kinase domain and its signaling. Similarly, active Erks can also phosphorylate multiple threonine residues in the docking protein FGF rec...
4 CitationsSource
#1Magdalena Lipok (UWr: University of Wrocław)H-Index: 1
#2Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
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: Overexpression of fibroblast growth factor receptor 1 (FGFR1) is a common aberration in lung and breast cancers and has necessitated the design of drugs targeting FGFR1-dependent downstream signaling and FGFR1 ligand binding. To date, the major group of drugs being developed for treatment of FGFR1-dependent cancers are small-molecule tyrosine kinase inhibitors; however, the limited specificity of these drugs has led to increasing attempts to design molecules targeting the extracellular domain ...
6 CitationsSource
#1Natalia Porębska (UWr: University of Wrocław)H-Index: 3
#2Marta Latko (UWr: University of Wrocław)H-Index: 3
Last. Łukasz Opaliński (UWr: University of Wrocław)H-Index: 7
view all 6 authors...
Fibroblast growth factor receptors (FGFRs) in response to fibroblast growth factors (FGFs) transmit signals across the cell membrane, regulating important cellular processes, like differentiation, division, motility, and death. The aberrant activity of FGFRs is often observed in various diseases, especially in cancer. The uncontrolled FGFRs’ function may result from their overproduction, activating mutations, or generation of FGFRs’ fusion proteins. Besides their typical subcellular localization...
31 CitationsSource
It has been brought to our attention that the affiliation of Dr. Jerzy Pieczykolan at the time when he was responsible for the work described in the paper [...]
Source
#1Michal Kostas (Oslo University Hospital)H-Index: 1
#2Agata Lampart (UWr: University of Wrocław)H-Index: 2
Last. Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
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Abstract FGF1 and FGF2 bind to specific cell-surface tyrosine kinase receptors (FGFRs) and activate intracellular signaling that leads to proliferation, migration or differentiation of many cell types. Besides this classical mode of action, under stress conditions, FGF1 and FGF2 are translocated in a receptor-dependent manner via the endosomal membrane into the cytosol and nucleus of the cell. However, despite many years of research, the role of translocated FGF1 and FGF2 inside the cell remains...
10 CitationsSource
#1Julia Chudzian (UWr: University of Wrocław)H-Index: 2
#2Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 7 authors...
Fibroblast growth factor 1 (FGF1) and its receptors (FGFRs) regulate crucial biological processes such as cell proliferation and differentiation. Aberrant activation of FGFRs by their ligands can promote tumor growth and angiogenesis in many tumor types, including lung or breast cancer. The development of FGF1-targeting molecules with potential implications for the therapy of FGF1-driven tumors is recently being considered a promising approach in the treatment of cancer. In this study we have us...
2 CitationsSource