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A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome

Nathalie Neyroud
Frédérique Tesson
Pascale Guicheney
Research01 Feb 1997
Nature Genetics

Volume: 15, P: 186-189
Structural mapping of PEAK pseudokinase interactions identifies 14-3-3 as a molecular switch for PEAK3 signaling

The PEAK family of pseudokinases are key hubs in cellular signalling, including cell motility and cancer. Here, the authors characterise how PEAK proteins interact with the adapter proteins CrkII and Grb2 and regulatory scaffold protein 14-3-3, to achieve functional signalling assemblies.

Michael J. Roy
Minglyanna G. Surudoi
Isabelle S. Lucet
ResearchOpen Access19 Jun 2023
Nature Communications

Volume: 14, P: 1-19
Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and heterotypic association

Pseudokinases lack kinase activity, yet they impact cellular physiology through the regulation of bona fide signaling kinases. Here the authors describe the structure of the SgK223 pseudokinase and its adjacent domains, and identify regulatory interfaces required for self-assembly and downstream signaling.

Onisha Patel
Michael D. W. Griffin
Isabelle S. Lucet
ResearchOpen Access27 Oct 2017
Nature Communications

Volume: 8, P: 1-15
Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix

The viral Protein Kinase-1 (PK-1) phosphorylates the regulatory protein p6.9, which facilitates baculoviral genome release. Here, the authors combine X-ray crystallography with biophysical and biochemical analyses as well as molecular dynamics simulations to characterize Cydia pomenella granulovirus PK-1, which forms a dimer with a parallel side-to-side arrangement of the kinase domains and furthermore, they provide insights into its catalytic mechanism and evolutionary relationships with other kinases.

Michael R. Oliver
Christopher R. Horne
James M. Murphy
ResearchOpen Access12 Feb 2021
Nature Communications

Volume: 12, P: 1-11
Distinct pseudokinase domain conformations underlie divergent activation mechanisms among vertebrate MLKL orthologues

The necroptotic cell death pathway involves signaling through pseudokinases. Here the authors define the structural determinants of species specificity in necroptosis signaling mediated by the essential necroptotic effector pseudokinase, Mixed Lineage Kinase Domain-Like (MLKL).

Katherine A. Davies
Cheree Fitzgibbon
James M. Murphy
ResearchOpen Access19 Jun 2020
Nature Communications

Volume: 11, P: 1-11
Co-clustering of EphB6 and ephrinB1 in trans restrains cancer cell invasion

This study demonstrates that co-clustering of the EphB6 receptor tyrosine pseudokinase with its ephrinB1 ligand on neighboring cells promotes formation of intercellular tubules. This stabilizes cell-cell adhesion and reduces cancer cell invasion.

Lung-Yu Liang
Niall D. Geoghegan
Isabelle S. Lucet
ResearchOpen Access16 Apr 2024
Communications Biology

Volume: 7, P: 1-13
Ubiquitylation of MLKL at lysine 219 positively regulates necroptosis-induced tissue injury and pathogen clearance

Necroptosis is a form of cell death characterized by membrane rupture via MLKL oligomerization, although mechanistic details remain unclear. Here, the authors show that MLKL ubiquitylation of K219 facilitates high-order membrane assembly and subsequent rupture, promoting cytotoxicity.

Laura Ramos Garcia
Tencho Tenev
Pascal Meier
ResearchOpen Access07 Jun 2021
Nature Communications

Volume: 12, P: 1-18
Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis

RIPK3-mediated phosphorylation of the mixed lineage kinase domain-like (MLKL) pseudokinase is thought to be the trigger for MLKL activation during necroptotic signaling. Here the authors provide evidence that the transition of human MLKL from a monomeric state to a tetramer is essential for necroptosis signalling.

Emma J. Petrie
Jarrod J. Sandow
James M. Murphy
ResearchOpen Access21 Jun 2018
Nature Communications

Volume: 9, P: 1-15
The molecular basis of JAK/STAT inhibition by SOCS1

Cytokines are key molecules in controlling haematopoiesis that signal via the JAK/STAT pathway. Here the authors present the structures of SOCS1 bound to its JAK1 target as well as in complex with elonginB and elonginC, providing a molecular explanation for the potent JAK- inhibitory activity of SOCS1.

Nicholas P. D. Liau
Artem Laktyushin
Jeffrey J. Babon
ResearchOpen Access19 Apr 2018
Nature Communications

Volume: 9, P: 1-14
SOCS3 binds specific receptor–JAK complexes to control cytokine signaling by direct kinase inhibition

The inhibitory protein SOCS3 plays a key part in hematopoiesis by regulating signaling induced by specific cytokines. The crystal structure of SOCS3 bound to JAK2 and a fragment of the interleulkin-6 receptor reveals how SOCS3 targets specific receptor–JAK complexes and how it exerts its inhibitory activity by blocking substrate binding.

Nadia J Kershaw
James M Murphy
Jeffrey J Babon
Research03 Mar 2013
Nature Structural & Molecular Biology

Volume: 20, P: 469-476
At-admission prediction of mortality and pulmonary embolism in an international cohort of hospitalised patients with COVID-19 using statistical and machine learning methods

Munib Mesinovic
Xin Ci Wong
David Zucman
ResearchOpen Access16 Jul 2024
Scientific Reports

Volume: 14, P: 1-43
Structural basis for small molecule targeting of Doublecortin Like Kinase 1 with DCLK1-IN-1

Patel et al. report crystal structures of the kinase domain of Doublecortin-like kinase 1 (DCLK1) in complex with a potent inhibitor and its precursors. Their structural study reveals insights into the mode of action of the inhibitor DCLK1-IN-1 and sets the basis for the design of isoform-specific inhibitors of DCLK1, which plays a role in tumour growth and development.

Onisha Patel
Michael J. Roy
Isabelle S. Lucet
ResearchOpen Access20 Sept 2021
Communications Biology

Volume: 4, P: 1-13
Mapping and functional analysis of heterochromatin protein 1 phosphorylation in the malaria parasite Plasmodium falciparum

Hai T. N. Bui
Igor Niederwieser
Till S. Voss
ResearchOpen Access13 Nov 2019
Scientific Reports

Volume: 9, P: 1-15
Hierarchical phosphorylation of apical membrane antigen 1 is required for efficient red blood cell invasion by malaria parasites

Boris Prinz
Katherine L. Harvey
Tim W. Gilberger
ResearchOpen Access04 Oct 2016
Scientific Reports

Volume: 6, P: 1-12
ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

Ali Abbas
Sheryl Ann Abdukahil
Luis Felipe Reyes
ResearchOpen Access30 Jul 2022
Scientific Data

Volume: 9, P: 1-22
Eph receptor signalling: from catalytic to non-catalytic functions

Lung-Yu Liang
Onisha Patel
Isabelle S. Lucet
ReviewsOpen Access12 Aug 2019
Oncogene

Volume: 38, P: 6567-6584

Search

A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome

Structural mapping of PEAK pseudokinase interactions identifies 14-3-3 as a molecular switch for PEAK3 signaling

Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and heterotypic association

Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix

Distinct pseudokinase domain conformations underlie divergent activation mechanisms among vertebrate MLKL orthologues

Co-clustering of EphB6 and ephrinB1 in trans restrains cancer cell invasion

Ubiquitylation of MLKL at lysine 219 positively regulates necroptosis-induced tissue injury and pathogen clearance

Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis

The molecular basis of JAK/STAT inhibition by SOCS1

SOCS3 binds specific receptor–JAK complexes to control cytokine signaling by direct kinase inhibition

At-admission prediction of mortality and pulmonary embolism in an international cohort of hospitalised patients with COVID-19 using statistical and machine learning methods

Structural basis for small molecule targeting of Doublecortin Like Kinase 1 with DCLK1-IN-1

Mapping and functional analysis of heterochromatin protein 1 phosphorylation in the malaria parasite Plasmodium falciparum

Hierarchical phosphorylation of apical membrane antigen 1 is required for efficient red blood cell invasion by malaria parasites

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

Eph receptor signalling: from catalytic to non-catalytic functions

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