Publications related to Janus kinase

The role of LRRK2 in lung adenocarcinoma

Lung cancer is the leading cause of cancer-related deaths worldwide and the most common lung cancer subtype is lung adenocarcinoma (LUAD). Frequently mutated genes involve activating mutations in KRAS and loss of function mutations in TP53. LUADs primarily ...

EPFL2024

Structural basis of Focal Adhesion Kinase activation on lipid membranes

Henning Paul-Julius Stahlberg, Frauke Gräter

Focal adhesion kinase (FAK) is a key component of the membrane proximal signaling layer in focal adhesion complexes, regulating important cellular processes, including cell migration, proliferation, and survival. In the cytosol, FAK adopts an autoinhibited ...

2020

Centriole foci persist in starfish oocytes despite Polo-like kinase 1 inactivation or loss of microtubule nucleation activity

Pierre Gönczy, Nils Kalbfuss, Marie Juliette Ségolène Pierron

Centrioles must be eliminated or inactivated from the oocyte to ensure that only the two functional centrioles contributed by the sperm are present in the zygote. Such removal can occur during oogenesis, as in Drosophila, where departure of Polo kinase fro ...

2020

Allosteric regulation and targeting of Bruton's tyrosine kinase (Btk) in B-cell lymphoma

Daniel Pereira Duarte

Bruton's tyrosine kinase (Btk) is a key component of BCR signaling required for B-cell maturation and activation. Loss-of-function mutations throughout the Btk protein cause human X-linked agammaglobulinemia (XLA), a heritable genetic disorder characterize ...

EPFL2020

Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase signaling in cardiac myocytes by oxidizing agents

Sonia Donzelli

The contraction and relaxation of the heart is controlled by stimulation of the beta 1-adrenoreceptor (AR) signaling cascade, which leads to activation of cAMP-dependent protein kinase (PKA) and subsequent cardiac protein phosphorylation. Phosphorylation i ...

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC2020

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

Autophagy and LRRK2 in the Aging Brain

Salvatore Novello

Autophagy is a highly conserved process by which long-lived macromolecules, protein aggregates and dysfunctional/damaged organelles are delivered to lysosomes for degradation. Autophagy plays a crucial role in regulating protein quality control and cell ho ...

FRONTIERS MEDIA SA2019

Live imaging screen reveals that TYRO3 and GAK ensure accurate spindle positioning in human cells

Pierre Gönczy, Coralie Busso, Benita Wolf

Proper spindle positioning is crucial for spatial cell division control. Spindle positioning in human cells relies on a ternary complex comprising G alpha i1-3, LGN and NuMA, which anchors dynein at the cell cortex, thus enabling pulling forces to be exert ...

Springer2019

Rapid Screen for Tyrosine Kinase Inhibitor Resistance Mutations and Substrate Specificity

Sandrine Madeleine Suzanne Georgeon, Oliver Hantschel, Sina Maren Reckel

We present a rapid and high-throughput yeast and flow cytometry based method for predicting kinase inhibitor resistance mutations and determining kinase peptide substrate specificity. Despite the widespread success of targeted kinase inhibitors as cancer t ...

AMER CHEMICAL SOC2019

Transmembrane Prolines Mediate Signal Sensing and Decoding in Bacillus subtilis DesK Histidine Kinase

Matteo Dal Peraro, Luciano Andres Abriata

Environmental awareness is an essential attribute of all organisms. The homeoviscous adaptation system of Bacillus subtilis provides a powerful experimental model for the investigation of stimulus detection and signaling mechanisms at the molecular level. ...

2019

Identification of novel PCTAIRE-1/CDK16 substrates using a chemical genetic screen

Kei Sakamoto, Caterina Collodet, Maria Deak

PCTAIRE-1 (also known as cyclin-dependent protein kinase (CDK) 16), is a Ser/Thr kinase that has been implicated in many cellular processes, including cell cycle, spermatogenesis, neurite outgrowth, and vesicle trafficking. Most recently, it has been propo ...

2019

The endosomal sorting adaptor HD-PTP is required for ephrin-B: EphB signalling in cellular collapse and spinal motor axon guidance

Daniel Eduardo Morales Garza

The signalling output of many transmembrane receptors that mediate cell-cell communication is restricted by the endosomal sorting complex required for transport (ESCRT), but the impact of this machinery on Eph tyrosine kinase receptor function is unknown. ...

Nature Research2019

Cytosolic delivery and characterization of monobodies interfering with SH2 domain-phosphotyrosine interactions

Nadine Eliane Schmit

Targeted cancer therapy is a very promising concept; however, small molecule inhibitors only exist for a limited number of oncoproteins and resistance development limits their clinical use. Different engineered non-antibody scaffolds are being explored to ...

EPFL2018

Janus nanostructures for heterogeneous photocatalysis

Monisha Rastogi

Water treatment, the hydrogen evolution reaction, and carbon capture are examples of the potential applications for solar photocatalysis. This has led to significant effort in the search for suitable heterogeneous catalysts. However, materials developed to ...

2018

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

Cell culture-based biosensing techniques for detecting toxicity in water

The significant increase of contaminants entering fresh water bodies calls for the development of rapid and reliable methods to monitor the aquatic environment and to detect water toxicity. Cell culture-based biosensing techniques utilise the overall cytot ...

Elsevier2017

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

Physiological regulation of the CDK16/PCTAIRE-1 protein kinase and its proposed role in the brain

Saifeldin Nasser Mohamed Ibrahim Shehata

Cell signalling, mediated to a large extent by protein kinase phosphorylation, plays a vital role in regulation of cellular function. PCTAIRE-1 (also known as cyclin-dependent protein kinase (CDK)16), is a Ser/Thr kinase that has been implicated in many ce ...

EPFL2017

Allosteric kinase inhibitors

Oliver Hantschel

Background. Inhibition of the kinase activity of the BCR-ABL1 oncoprotein by an allosteric mechanism of action facilitates alternative treatment options for chronic myeloid leukemia (CML) patients who cannot be adequately treated with conventional catalyti ...

Springer Nature2017

Kinase-templated abiotic reaction

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon

Protein kinases are quintessential regulators of cellular function. Numerous pathologies are intimately linked to the dysregulated activity of a particular protein kinase. Herein we report a technology based on a proximity-induced chemical transformation t ...

2017