Condensed-phase signaling can expand kinase specificity and respond to macromolecular crowding

Sang, Dajun; Shu, Tong; Pantoja, Christian F.; Opakua, Alain Ibáñez de; Zweckstetter, Markus; Holt, Liam J.

doi:10.1016/j.molcel.2022.08.016

Cited by 55 publications

(34 citation statements)

References 79 publications

(124 reference statements)

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“…A small amount of reactant then went further towards revving up enzymatic action, allowing greater catalytic efficiency overall. An independent study published in September demonstrated this same scaffolding effect with a broad array of enzymes 2 .…”

Section: Form and Functionmentioning

confidence: 74%

The shape-shifting blobs that shook up cell biology

Dolgin¹

2022

Nature

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For years, if you asked a scientist how they pictured the inner workings of a cell, they might have spoken of a highly organized factory, with different departments each performing specialized tasks in delineated assembly lines.Ask now, and they might be more inclined to compare the cell to a chaotic openplan office, with hot-desking zones where different types of cellular matter gather to complete a task and then scatter to other regions.Everywhere scientists look in cells, throngs of proteins and RNA seem to be sticking together, coalescing into pearl-like droplets distinct from their surrounding environment. These dynamic compartments allow cells to perform essential functions, ranging from gene control and DNA repair to waste disposal and stress responses. They are often fleeting, and are unhindered by an enclosing membrane -unlike many other cellular components, such as mitochondria, which are membrane-bound. When a droplet is no longer needed, it vanishes.These transient beads are created by a MARINA FERIC & CLIFF BRANGWYNNECondensates (red, green, blue) containing proteins nest within one another in this fragment of a nucleus from a frog cell.

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Section: Form and Functionmentioning

confidence: 74%

The shape-shifting blobs that shook up cell biology

Dolgin¹

2022

Nature

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“…Similarly, regulated clustering of bacterial kinases such as C. crescentus DivJ can activate downstream signals ( 40 ). Recent work has identified aspects of condensed-phase signaling within multiprotein clusters that promote signal transduction in phosphorylation pathways ( 41 ). This widespread phenomenon makes kinase clustering an attractive candidate for synthetic biology approaches that seek to control signaling networks ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Regulation of cell size and Wee1 kinase by elevated levels of the cell cycle regulatory protein kinase Cdr2

Berg¹,

Moseley²

2023

Journal of Biological Chemistry

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“…Meanwhile, PS can produce membrane‐free biomolecular condensates, in which specific biomolecules are concentrated and serve biological functions 3 . For instance, the phosphorylation of the Alzheimer's disease‐related protein tau by cyclin‐dependent kinase 2 is accelerated in condensates, 4 and biomolecular condensates are implicated in the regulation of postsynaptic density at neuronal synapses in synaptic signaling and plasticity 3 . Numerous studies have demonstrated the significance of biomolecular condensates in physiology and pathophysiology 2,3 .…”

Section: Figurementioning

confidence: 99%