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Welcome to BJ Signal

Discover what's new and interesting in all aspects of signalling

The JAK (Janus kinase) family, comprising members such as JAK1, JAK2, JAK3 and TYK2 (tyrosine kinase 2), serve essential roles as the intracellular signalling effectors of cytokine receptors. In this review, James Murphy and colleagues review the current knowledge of their physiological functions and the causative role of activating and inactivating JAK mutations in human diseases, including haemopoietic malignancies, immunodeficiency and inflammatory diseases. They discuss recent studies that have highlighted the diversity of regulatory mechanisms utilized by the JAK family to maintain signalling fidelity, and suggest alternative therapeutic strategies that will complement existing ATP-competitive kinase inhibitors.
GPR39 is a G-protein-coupled zinc receptor that protects against diverse effectors of cell death. In this paper, Axel Methner and colleagues show how PKIβ (protein kinase A inhibitor β), identified as an interacting protein of GPR39 via a yeast two-hybrid screen, increases its cytoprotective constitutive activity via Gα13, but has no effect on ligand-mediated activation of Gs and Gq regardless of its inhibitory activity on protein kinase A.
IKKβ {IĸB [inhibitor of NF-ĸB (nuclear factor ĸB)] kinase β} is required to activate the transcription factor NF-ĸB, but how IKKβ itself is activated in vivo is still unclear: some reports have proposed phosphorylation by one or more 'upstream' protein kinases, whereas other have suggested a mechanism of autophosphorylation. In this open access paper, Philip Cohen and colleagues have resolved this controversy by demonstrating that the activation of IKKβ induced by IL-1 (interleukin-1) or TNF (tumour necrosis factor) in embryonic fibroblasts, or by ligands that activate Toll-like receptors in macrophages, requires two distinct phosphorylation events: first, the TAK1 [TGFβ (transforming growth factor β)-activated kinase-1]-catalysed phosphorylation of Ser177 and, secondly, the IKKβ-catalysed autophosphorylation of Ser181.
Overactivation of immune pathways in obesity is an important cause of insulin resistance, and thus novel approaches aimed towards limiting inflammation or its consequences may be effective for treating Type 2 diabetes. In this review, Greg Steinberg and colleagues discuss the role of SOCS1 (suppressor of cytokine signalling 1) and SOCS3 in controlling immune cells such as macrophages and T-cells, and the impact this can have on systemic inflammation and insulin resistance. They also dissect the mechanisms by which SOCS (1-7) regulate insulin signalling in different tissues, and show how findings from SOCS whole-body and tissue-specific null mice have implicated an important role for these proteins in controlling insulin action and glucose homoeostasis in obesity.
Content in BJ Signal
2014 - Volumes 457-464
  • Volume 462
2013 - Volumes 449-456
2012 - Volumes 441-448
  • Volume 448
    • part 3, 297-423 (15 Dec)
    • part 2, 171-295 (1 Dec)
    • part 1, 1-169 (15 Nov)
2011 - Volumes 433-440
2010 - Volumes 425-432
  • Volume 430
    • part 3, 365-599 (15 Sep)
    • part 2, 179-364 (1 Sep)
    • part 1, 1-177 (15 Aug)
2009 - Volumes 417-424
2008 - Volumes 409-416
2007 - Volumes 401-408
2006 - Volumes 393-400
2005 - Volumes 385-392
2004 - Volumes 377-384
2003 - Volumes 369-376
  • Volume 369
    • part 3, 429-739 (1 Feb)
    • part 2, 199-427 (15 Jan)
    • part 1, 1-198 (1 Jan)
2002 - Volumes 361-368