Mapping phospho-catalytic dependencies of therapy-resistant tumours reveals actionable vulnerabilities.
3-Phosphoinositide-Dependent Protein Kinases
/ genetics
Adult
Aged
Cell Line, Tumor
Colorectal Neoplasms
/ drug therapy
Drug Resistance, Neoplasm
/ genetics
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Indoles
/ chemistry
Kaplan-Meier Estimate
MAP Kinase Signaling System
/ genetics
Male
Melanoma
/ drug therapy
Middle Aged
Peptides
/ chemistry
Phosphorylation
/ drug effects
Protein Kinase C-alpha
/ genetics
Protein Kinase Inhibitors
/ therapeutic use
Proto-Oncogene Proteins c-pim-1
/ genetics
Sulfonamides
/ therapeutic use
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
30
03
2018
accepted:
09
04
2019
entrez:
5
6
2019
pubmed:
5
6
2019
medline:
10
7
2019
Statut:
ppublish
Résumé
Phosphorylation networks intimately regulate mechanisms of response to therapies. Mapping the phospho-catalytic profile of kinases in cells or tissues remains a challenge. Here, we introduce a practical high-throughput system to measure the enzymatic activity of kinases using biological peptide targets as phospho-sensors to reveal kinase dependencies in tumour biopsies and cell lines. A 228-peptide screen was developed to detect the activity of >60 kinases, including ABLs, AKTs, CDKs and MAPKs. Focusing on BRAF
Identifiants
pubmed: 31160710
doi: 10.1038/s41556-019-0328-z
pii: 10.1038/s41556-019-0328-z
pmc: PMC7170003
mid: NIHMS1571894
doi:
Substances chimiques
Indoles
0
Peptides
0
Protein Kinase Inhibitors
0
Sulfonamides
0
3-Phosphoinositide-Dependent Protein Kinases
EC 2.7.11.1
PDPK1 protein, human
EC 2.7.11.1
PIM1 protein, human
EC 2.7.11.1
Proto-Oncogene Proteins c-pim-1
EC 2.7.11.1
PRKCA protein, human
EC 2.7.11.13
Protein Kinase C-alpha
EC 2.7.11.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
778-790Subventions
Organisme : NCI NIH HHS
ID : R01 CA122216
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209891
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000005
Pays : United States
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