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The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

Publications associées (57)

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Structure and regulation of the myotonic dystrophy kinase-related Cdc42-binding kinase

Charlotte Julie Caroline Gehin

Protein kinases of the dystonia myotonica protein kinase (DMPK) family are critical regulators of actomyosin contractility in cells. The DMPK kinase MRCK1 is required for the activation of myosin, leading to the develop-ment of cortical tension, apical con ...

CELL PRESS2023

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

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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

Phosphorylation of the overlooked tyrosine 310 regulates the structure, aggregation, and microtubule- and lipid-binding properties of Tau

Hilal Lashuel, Nadine Aït Bouziad, Anass Chiki, Galina Limorenko

The microtubule-associated protein Tau is implicated in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. Increasing evidence suggests that post-translational modifications play critical roles in regulating Tau's norma ...

2020

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Off-target effects continue to impede disease interventions, particularly when targeting a specific protein within a family of similar proteins, such as kinase isoforms that play tumor-subtype-specific roles in cancers. Exploiting the specific electrophili ...

AMER CHEMICAL SOC2020

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

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

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

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

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

Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics

Romain Hamelin, Sandrine Madeleine Suzanne Georgeon, Oliver Hantschel, Sina Maren Reckel

The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphobl ...

Nature Publishing Group2017