Arrestins as Regulatory Hubs in Cancer Signalling Pathways
Non-visual arrestins were initially appreciated for the roles they play in the negative regulation of G protein-coupled receptors through the processes of desensitisation and endocytosis. The arrestins are also now known as protein scaffolding platforms t
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Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 β-Arrestin Expression Levels in Human Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 β-Arrestin Levels in Human Breast Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 β-Arrestin Levels in Other Types of Human Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 β-Arrestin Scaffolds in Cancer Signalling Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 β-arr–Src Scaffolds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 β-arr Scaffolds in the PTEN/PI3K/AKT Pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 β-arr Scaffolds Controlling Mdm2/p53 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 β-arr Scaffolds Controlling β-Catenin Signalling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Non-visual arrestins were initially appreciated for the roles they play in the negative regulation of G protein-coupled receptors through the processes of desensitisation and endocytosis. The arrestins are also now known as protein scaffolding platforms that act downstream of multiple types of receptors, ensuring relevant transmission of information for an appropriate cellular response. They function as regulatory hubs in several important signalling pathways that are often H. Enslen (*) • M.G.H. Scott (*) Inserm, U1016, Institut Cochin, 27, Rue du Faubourg Saint Jacques, 75014 Paris, France CNRS, UMR8104, Paris, France Univ. Paris Descartes, Sorbonne Paris Cite´, Paris, France e-mail: [email protected]; [email protected] E. Lima-Fernandes Inserm, U1016, Institut Cochin, 27, Rue du Faubourg Saint Jacques, 75014 Paris, France CNRS, UMR8104, Paris, France Univ. Paris Descartes, Sorbonne Paris Cite´, Paris, France Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada V.V. Gurevich (ed.), Arrestins - Pharmacology and Therapeutic Potential, Handbook of Experimental Pharmacology 219, DOI 10.1007/978-3-642-41199-1_21, © Springer-Verlag Berlin Heidelberg 2014
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dysregulated in human cancers. Interestingly, several recent studies have documented changes in expression and localisation of arrestins that occur during cancer progression and that corre
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