Publications de Tim Kükenshöner

Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B-cell neoplasms

Matteo Dal Peraro, Florence Pojer, Sandrine Madeleine Suzanne Georgeon, Maria Josefina Marcaida Lopez, Oliver Hantschel, Allan Joaquim Lamontanara, Tim Kükenshöner, Daniel Pereira Duarte, Grégory La Sala

Bruton's tyrosine kinase (Btk) is critical for B-cell maturation and activation. Btk loss-of-function mutations cause human X-linked agammaglobulinemia (XLA). In contrast, Btk signaling sustains growth of several B-cell neoplasms which may be treated with ...

Nature Publishing Group2020

Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains

Florence Pojer, Kelvin Ka Ching Lau, Oliver Hantschel, Tim Kükenshöner, Grégory La Sala

The transcription factor STAT3 is frequently activated in human solid and hematological malignancies and remains a challenging therapeutic target with no approved drugs to date. Here, we develop synthetic antibody mimetics, termed monobodies, to interfere ...

Nature Research2020

Development of Mirror-Image Monobodies for Targeted Cancer Therapies

Oliver Hantschel, Tim Kükenshöner, Timothy Matthias Reichart

WILEY2018

Selective Targeting of SH2 Domain–Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies

Florence Pojer, Oliver Hantschel, Nadine Eliane Schmit, Tim Kükenshöner

The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Src family kinases (SFKs). The high sequence conservation of the 120 human SH2 domains poses a significant c ...

Elsevier2017

Unpaired extracellular cysteine mutations of CSF3R mediate gain or loss of function

Oliver Hantschel, Tim Kükenshöner

Exclusive of membrane-proximal mutations seen commonly in chronic neutrophilic leukemia (e.g. T618I), functionally defective mutations in the extracellular domain of the granulocyte colony-stimulating factor receptor (CSF3R) have been reported only in seve ...

American Association for Cancer Research2017

Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase

Florence Pojer, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Barbara Gerig, Charlotte Julie Caroline Gehin, Sina Maren Reckel, Tim Kükenshöner, Delphine Maude Tardivon, Sara Raquel Pereira Pinho

The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study ...

Springer Nature2017