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

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.
NUAK1 (NUAK family SnF1-like kinase-1) and NUAK2 protein kinases are activated by the LKB1 tumour suppressor and have been implicated in regulating multiple processes such as cell survival, senescence, adhesion and polarity. In this paper, Sourav Banerjee, Dario Alessi and colleagues have investigated how the NUAK isoforms are biologically regulated, and their results highlight the remarkable interplay that exists between PLK (Polo kinase), NUAK1, the PP1βMYPT1 phosphatase and SCFβTrCP (Skp, Cullin and F-boxβTrCP) signalling components. They also show how NUAK1 inhibitors suppress cell proliferation and PLK1.
Macroautophagy is a physiological cellular response to nutrient stress, which leads to the engulfment of cytosolic contents by a double-walled membrane structure, the phagophore; phagophores subsequently seal to become autophagosomes, which then fuse with lysosomes to deliver their contents for degradation. Vps34 (vacuolar protein sorting 34) is a cellular factor whose autophagic function requires its recruitment to a complex known as Vps34 Complex I. In this paper, Jonathan Backer and colleagues show that NRBF2 (nuclear receptor-binding factor 2) is a member of Vps34 Complex I, which includes Vps34, Vps15, Beclin-1 and Atg14L, but not the Complex II component UVRAG (UV radiation resistance-associated gene). NRBF2 binds directly to Vps15 and is required for autophagy initiation in starved cells.
Content in BJ Signal
2014 - Volumes 457-464
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