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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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An overview of the fission yeast septation initiation network (SIN)

Viesturs Simanis, Andrea Krapp

The fission yeast septation initiation network, or SIN, is a signal transduction network that is required for septum formation in Schizosaccharomyces pombe. Its activity is tightly regulated through the cell cycle, to ensure proper co-ordination of mitosis ...

2008

Structures of P. falciparum protein kinase 7 identify an activation motif and leads for inhibitor design

Malaria is a major threat to world health. The identification of parasite targets for drug development is a priority and parasitic protein kinases suggest themselves as suitable targets as many display profound structural and functional divergences from th ...

2008

The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib

Oliver Hantschel

Dasatinib is a small-molecule kinase inhibitor used for the treatment of imatinib-resistant chronic myelogenous leukemia (CML). We have analyzed the kinases targeted by dasatinib by using an unbiased chemical proteomics approach to detect binding proteins ...

National Academy of Sciences2007

Notch-induced T cell development requires phosphoinositide-dependent kinase 1

Freddy Radtke

Phosphoinositide-dependent kinase l (PDK1) phosphorylates and activates multiple AGC serine kinases, including protein kinase B (PKB), p70Ribosomal S6 kinase (S6K) and p90Ribosomal S6 kinase (RSK). PDK1 is required for thymocyte differentiation and prolife ...

2007

Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase

Oliver Hantschel

The tyrosine kinase c-Abl is inactivated by interactions made by its SH3 and SH2 domains with the distal surface of the kinase domain. We present a crystal structure of a fragment of c-Abl which reveals that a critical N-terminal cap segment, not visualize ...

Elsevier2006

Conserved autophosphorylation pattern in activation loops and juxtamembrane regions of Mycobacterium tuberculosis Ser/Thr protein kinases

Stewart Cole, Pablo Fernandez

The identification of phosphorylation sites in proteins provides a powerful tool to study signal transduction pathways and to establish interaction networks involving signaling elements. Using different strategies to identify phosphorylated residues, we re ...

2005

The surge of interest in protein kinases as targets for chemotherapeutic intervention in a number of diseases such as cancer and neurodegenerative disorders has stimulated research aimed at determining whether enzymes of this class might also be considered ...

2005

The Bcr-Abl tyrosine kinase causes different forms of leukemia in humans. Depending on its position within the cell, Bcr-Abl differentially affects cellular growth. However, no structural and molecular details for the anticipated localization determinants ...

Elsevier2005

The prototypic non-receptor tyrosine kinase c-Abl is implicated in various cellular processes. Its oncogenic counterpart, the Bcr-Abl fusion protein, causes certain human leukaemias. Recent insights into the structure and regulation of the c-Abl and Bcr-Ab ...

Nature Publishing Group2004

The c-Abl tyrosine kinase is inhibited by mechanisms that are poorly understood. Disruption of these mechanisms in the Bcr-Abl oncoprotein leads to several forms of human leukemia. We found that like Src kinases, c-Abl 1b is activated by phosphotyrosine li ...

Elsevier2003