Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer.
Science
; 384(6700): eadk0850, 2024 Jun 07.
Article
de En
| MEDLINE
| ID: mdl-38843329
ABSTRACT
To delineate the mechanisms by which the ERK1 and ERK2 mitogen-activated protein kinases support mutant KRAS-driven cancer growth, we determined the ERK-dependent phosphoproteome in KRAS-mutant pancreatic cancer. We determined that ERK1 and ERK2 share near-identical signaling and transforming outputs and that the KRAS-regulated phosphoproteome is driven nearly completely by ERK. We identified 4666 ERK-dependent phosphosites on 2123 proteins, of which 79 and 66%, respectively, were not previously associated with ERK, substantially expanding the depth and breadth of ERK-dependent phosphorylation events and revealing a considerably more complex function for ERK in cancer. We established that ERK controls a highly dynamic and complex phosphoproteome that converges on cyclin-dependent kinase regulation and RAS homolog guanosine triphosphatase function (RHO GTPase). Our findings establish the most comprehensive molecular portrait and mechanisms by which ERK drives KRAS-dependent pancreatic cancer growth.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du pancréas
/
Phosphoprotéines
/
Protéines proto-oncogènes p21(ras)
/
Mitogen-Activated Protein Kinase 1
/
Protéome
/
Mitogen-Activated Protein Kinase 3
Limites:
Animals
/
Humans
Langue:
En
Journal:
Sci. (N.Y., N.Y.)
/
Science
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique
Pays de publication:
États-Unis d'Amérique