Diseases caused by altered specificity of a protein kinase for its allosteric activators

Philip Cohen; Tom Snelling

doi:10.1016/j.tibs.2024.10.008

Diseases caused by altered specificity of a protein kinase for its allosteric activators

Philip Cohen (Lead / Corresponding author)
, Tom Snelling (Lead / Corresponding author)

MRC PPU

Research output: Contribution to journal › Review article › peer-review

5 Citations (Scopus)

81 Downloads (Pure)

Abstract

Protein kinases regulate many intracellular processes, and their dysregulation causes cancers and other diseases. This review focuses on the atypical alpha-kinase 1 (ALPK1), which is activated in mammalian cells by nucleoside diphosphate heptoses (ADP-heptose, UDP-heptose, and CDP-heptose) produced by microbial pathogens but not by mammalian cells. Mutations in human ALPK1 cause ROSAH syndrome and spiradenoma, which result from an alteration in its specificity for nucleoside diphosphate heptoses, causing aberrant activation by mammalian nucleoside diphosphate sugars without microbial infection. These may be the first diseases caused by altered specificity of an enzyme for its allosteric activators and has suggested ways in which selective drugs could be developed to treat them without compromising the innate immune system.

Original language	English
Pages (from-to)	61-70
Number of pages	10
Journal	Trends in Biochemical Sciences
Volume	50
Issue number	1
DOIs	https://doi.org/10.1016/j.tibs.2024.10.008
Publication status	Published - 2 Jan 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

ALPK1
ROSAH
spiradenoma
protein kinase
allosteric activator
nucleotide sugar

ASJC Scopus subject areas

Biochemistry
Molecular Biology

Access to Document

10.1016/j.tibs.2024.10.008Licence: CC BY

Final Published VersionFinal published version, 531 KBLicence: CC BY

Cite this

@article{db4cd4275f9a4e77bc341c761ae25c74,

title = "Diseases caused by altered specificity of a protein kinase for its allosteric activators",

abstract = "Protein kinases regulate many intracellular processes, and their dysregulation causes cancers and other diseases. This review focuses on the atypical alpha-kinase 1 (ALPK1), which is activated in mammalian cells by nucleoside diphosphate heptoses (ADP-heptose, UDP-heptose, and CDP-heptose) produced by microbial pathogens but not by mammalian cells. Mutations in human ALPK1 cause ROSAH syndrome and spiradenoma, which result from an alteration in its specificity for nucleoside diphosphate heptoses, causing aberrant activation by mammalian nucleoside diphosphate sugars without microbial infection. These may be the first diseases caused by altered specificity of an enzyme for its allosteric activators and has suggested ways in which selective drugs could be developed to treat them without compromising the innate immune system.",

keywords = "ALPK1, ROSAH, spiradenoma, protein kinase, allosteric activator, nucleotide sugar",

author = "Philip Cohen and Tom Snelling",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2025",

month = jan,

day = "2",

doi = "10.1016/j.tibs.2024.10.008",

language = "English",

volume = "50",

pages = "61--70",

journal = "Trends in Biochemical Sciences",

issn = "0968-0004",

publisher = "Elsevier",

number = "1",

}

TY - JOUR

T1 - Diseases caused by altered specificity of a protein kinase for its allosteric activators

AU - Cohen, Philip

AU - Snelling, Tom

PY - 2025/1/2

Y1 - 2025/1/2

N2 - Protein kinases regulate many intracellular processes, and their dysregulation causes cancers and other diseases. This review focuses on the atypical alpha-kinase 1 (ALPK1), which is activated in mammalian cells by nucleoside diphosphate heptoses (ADP-heptose, UDP-heptose, and CDP-heptose) produced by microbial pathogens but not by mammalian cells. Mutations in human ALPK1 cause ROSAH syndrome and spiradenoma, which result from an alteration in its specificity for nucleoside diphosphate heptoses, causing aberrant activation by mammalian nucleoside diphosphate sugars without microbial infection. These may be the first diseases caused by altered specificity of an enzyme for its allosteric activators and has suggested ways in which selective drugs could be developed to treat them without compromising the innate immune system.

AB - Protein kinases regulate many intracellular processes, and their dysregulation causes cancers and other diseases. This review focuses on the atypical alpha-kinase 1 (ALPK1), which is activated in mammalian cells by nucleoside diphosphate heptoses (ADP-heptose, UDP-heptose, and CDP-heptose) produced by microbial pathogens but not by mammalian cells. Mutations in human ALPK1 cause ROSAH syndrome and spiradenoma, which result from an alteration in its specificity for nucleoside diphosphate heptoses, causing aberrant activation by mammalian nucleoside diphosphate sugars without microbial infection. These may be the first diseases caused by altered specificity of an enzyme for its allosteric activators and has suggested ways in which selective drugs could be developed to treat them without compromising the innate immune system.

KW - ALPK1

KW - ROSAH

KW - spiradenoma

KW - protein kinase

KW - allosteric activator

KW - nucleotide sugar

UR - https://www.scopus.com/pages/publications/85210083199

U2 - 10.1016/j.tibs.2024.10.008

DO - 10.1016/j.tibs.2024.10.008

M3 - Review article

C2 - 39580356

SN - 0968-0004

VL - 50

SP - 61

EP - 70

JO - Trends in Biochemical Sciences

JF - Trends in Biochemical Sciences

IS - 1

ER -

Diseases caused by altered specificity of a protein kinase for its allosteric activators

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this