Functional proteomics to dissect tyrosine kinase signalling pathways in cancer

Advances in the generation and interpretation of proteomics data have spurred a transition from focusing on protein identification to functional analysis. Here we review recent proteomics results that have elucidated new aspects of the roles and regulation of signal transduction pathways in cancer using the epidermal growth factor receptor (EGFR), ERK and breakpoint cluster region (BCR)-ABL1 networks as examples. The emerging theme is to understand cancer signalling as networks of multiprotein machines which process information in a highly dynamic environment that is shaped by changing protein interactions and post-translational modifications (PTMs). Cancerous genetic mutations derange these protein networks in complex ways that are tractable by proteomics.

Analysis of oxidized and chlorinated lipids by mass spectrometry and relevance to signalling

Oxidized and chlorinated phospholipids are generated under inflammatory conditions and are increasingly understood to play important roles in diseases involving oxidative stress. MS is a sensitive and informative technique for monitoring phospholipid oxidation that can provide structural information and simultaneously detect a wide variety of oxidation products, including chain-shortened and -chlorinated phospholipids. MSn technologies involve fragmentation of the compounds to yield diagnostic fragment ions and thus assist in identification. Advanced methods such as neutral loss and precursor ion scanning can facilitate the analysis of specific oxidation products in complex biological samples. This is essential for determining the contributions of different phospholipid oxidation products in disease. While many pro-inflammatory signalling effects of oxPLs (oxidized phospholipids) have been reported, it has more recently become clear that they can also have anti-inflammatory effects in conditions such as infection and endotoxaemia. In contrast with free radical-generated oxPLs, the signalling effects of chlorinated lipids are much less well understood, but they appear to demonstrate mainly pro-inflammatory effects. Specific analysis of oxidized and chlorinated lipids and the determination of their molecular effects are crucial to understanding their role in disease pathology.

CNK1 scaffold protein and its role in the regulations of NF-KB signalling

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Non-verbal signalling in digital discourse:the case of letter repetition

This study focuses on the interactional functions of non-standard spelling, in particular letter repetition, used in text-based computer-mediated communication as a means of non-verbal signalling. The aim of this paper is to assess the current state of non-verbal cue research in computer-mediated discourse and demonstrate the need for a more comprehensive and methodologically rigorous exploration of written non-verbal signalling. The study proposes a contextual and usage-centered view of written paralanguage. Through illustrative, close linguistic analyses the study proves that previous approaches to non-standard spelling based on their relation to the spoken word might not account for the complexities of this CMC cue, and in order to further our understanding of their interactional functions it is more fruitful to describe the role they play during the contextualisation of the verbal messages. The interactional sociolinguistic approach taken in the analysis demonstrates the range of interactional functions letter repetition can achieve, including contribution to the inscription of socio-emotional information into writing, to the evoking of auditory cues or to a display of informality through using a relaxed writing style.