Kinase regulation by liquid-liquid phase separation.

Tania P López-Palacios, Joshua L Andersen

Journal: Trends in cell biology 2023;33(8):649-666

PMID: 36528418

Free Full Text on Elsevier Science View on PubMed

Abstract

Liquid-liquid phase separation (LLPS) is emerging as a mechanism of spatiotemporal regulation that could answer long-standing questions about how order is achieved in biochemical signaling. In this review we discuss how LLPS orchestrates kinase signaling, either by creating condensate structures that are sensed by kinases or by direct LLPS of kinases, cofactors, and substrates - thereby acting as a mechanism to compartmentalize kinase-substrate relationships, and in some cases also sequestering the kinase away from inhibitory factors. We also examine the possibility that selective pressure promotes genomic rearrangements that fuse pro-growth kinases to LLPS-prone protein sequences, which in turn drives aberrant kinase activation through LLPS.

Address: Fritz B. Burns Cancer Research Laboratory, Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.; Fritz B. Burns Cancer Research Laboratory, Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA. Electronic address: [email protected].

DOI: 10.1016/j.tcb.2022.11.009

Link outs

Free resources

Full Text Sources:

Subscription / membership required

Full Text Sources:

https://www.clinicalkey.com/content/playBy/pii?v=S...

MeSH Terms: Humans, Intrinsically Disordered Proteins, Amino Acid Sequence