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The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism.

• James M. Murphy, Peter E. Czabotar, +20 authors W. Alexander
• Immunity
• 2013

Mixed lineage kinase domain-like (MLKL) is a component of the "necrosome," the multiprotein complex that triggers tumor necrosis factor (TNF)-induced cell death by necroptosis. To define the specific… (More)

The molecular regulation of Janus kinase (JAK) activation.

• Jeffrey J Babon, Isabelle S Lucet, James M. Murphy, Nicos A. Nicola, Leila N. Varghese
• The Biochemical journal
• 2014

The JAK (Janus kinase) family members serve essential roles as the intracellular signalling effectors of cytokine receptors. This family, comprising JAK1, JAK2, JAK3 and TYK2 (tyrosine kinase 2), was… (More)

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

• Nadia J. Kershaw, James M. Murphy, +6 authors Jeffrey J Babon
• Nature Structural &Molecular Biology
• 2013

The inhibitory protein SOCS3 plays a key part in the immune and hematopoietic systems by regulating signaling induced by specific cytokines. SOCS3 functions by inhibiting the catalytic activity of… (More)

A robust methodology to subclassify pseudokinases based on their nucleotide-binding properties.

• James M. Murphy, Qingwei Zhang, +21 authors Isabelle S Lucet
• The Biochemical journal
• 2014

Protein kinase-like domains that lack conserved residues known to catalyse phosphoryl transfer, termed pseudokinases, have emerged as important signalling domains across all kingdoms of life.… (More)

Suppression of cytokine signaling by SOCS3: characterization of the mode of inhibition and the basis of its specificity.

• Jeffrey J Babon, Nadia J. Kershaw, +6 authors Nicos A. Nicola
• Immunity
• 2012

Janus kinases (JAKs) are key effectors in controlling immune responses and maintaining hematopoiesis. SOCS3 (suppressor of cytokine signaling-3) is a major regulator of JAK signaling and here we… (More)

Functional characterization of c-Mpl ectodomain mutations that underlie congenital amegakaryocytic thrombocytopenia.

• Leila N. Varghese, Jian-Guo Zhang, +5 authors James M. Murphy
• Growth factors
• 2014

Activation of the cell surface receptor, c-Mpl, by the cytokine, thrombopoietin (TPO), underpins megakaryocyte and platelet production in mammals. In humans, mutations in c-Mpl have been identified… (More)

An incomplete trafficking defect to the cell-surface leads to paradoxical thrombocytosis for human and murine MPL P106L.

• Fabrizia Favale, Kahia Messaoudi, +14 authors William Vainchenker
• Blood
• 2016

The mechanisms behind the hereditary thrombocytosis induced by the thrombopoietin (THPO) receptor MPL P106L mutant remain unknown. A complete trafficking defect to the cell surface has been reported,… (More)

The Thrombopoietin Receptor: Structural Basis of Traffic and Activation by Ligand, Mutations, Agonists, and Mutated Calreticulin

• Leila N. Varghese, J P Defour, Christian Pecquet, Stefan N. Constantinescu
• Front. Endocrinol.
• 2017

A well-functioning hematopoietic system requires a certain robustness and flexibility to maintain appropriate quantities of functional mature blood cells, such as red blood cells and platelets. This… (More)

Inhibition of IL-6 family cytokines by SOCS3.

• Jeffrey J Babon, Leila N. Varghese, Nicos A. Nicola
• Seminars in immunology
• 2014

IL-6 a multi-functional cytokine with important effects in both inflammation and haematopoiesis. SOCS3 is the primary inhibitor of IL-6 signalling, interacting with gp130, the common shared chain of… (More)

Mechanistic insights into activation and SOCS3-mediated inhibition of myeloproliferative neoplasm-associated JAK2 mutants from biochemical and structural analyses.

• Leila N. Varghese, Daniela Ungureanu, +8 authors James M. Murphy
• The Biochemical journal
• 2014

JAK2 (Janus kinase 2) initiates the intracellular signalling cascade downstream of cell surface receptor activation by cognate haemopoietic cytokines, including erythropoietin and thrombopoietin. The… (More)

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