Location, location, location: Protein kinase nanoclustering for optimised signalling output.
| Autor: | Gormal RS; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia., Martinez-Marmol R; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia., Brooks AJ; Frazer Institute, The University of Queensland, Woolloongabba, Australia., Meunier FA; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia.; School of Biomedical Sciences, The University of Queensland, St Lucia, Australia. |
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| Jazyk: | angličtina |
| Zdroj: | ELife [Elife] 2024 Jan 11; Vol. 13. Date of Electronic Publication: 2024 Jan 11. |
| DOI: | 10.7554/eLife.93902 |
| Abstrakt: | Protein kinases (PKs) are proteins at the core of cellular signalling and are thereby responsible for most cellular physiological processes and their regulations. As for all intracellular proteins, PKs are subjected to Brownian thermal energy that tends to homogenise their distribution throughout the volume of the cell. To access their substrates and perform their critical functions, PK localisation is therefore tightly regulated in space and time, relying upon a range of clustering mechanisms. These include post-translational modifications, protein-protein and protein-lipid interactions, as well as liquid-liquid phase separation, allowing spatial restriction and ultimately regulating access to their substrates. In this review, we will focus on key mechanisms mediating PK nanoclustering in physiological and pathophysiological processes. We propose that PK nanoclusters act as a cellular quantal unit of signalling output capable of integration and regulation in space and time. We will specifically outline the various super-resolution microscopy approaches currently used to elucidate the composition and mechanisms driving PK nanoscale clustering and explore the pathological consequences of altered kinase clustering in the context of neurodegenerative disorders, inflammation, and cancer. Competing Interests: RG, RM, AB, FM No competing interests declared (© 2024, Gormal et al.) |
| Databáze: | MEDLINE |
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