Skip to content
Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer
a graphic split into two parts by a diagonal light-blue line

On the left, taking up most of the image, is a teal background with the Science logo on the top left

Below is the white text "Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer".

At the bottom left, in capital letters, it says "Klomp et al."

On the smaller, right side of the image, is an abstract representation of red, glowing viruses next to DNA floating in blue space, with the word "publication" at the bottom in white, capital letters next to a paper icon

Researchers have conducted a comprehensive study to define the ways in which the ERK1 and ERK2 mitogen-activated protein kinases support mutant KRAS-driven cancer growth in pancreatic ductal adenocarcinoma (PDAC). Through quantitative phosphoproteomics, they identified 4,666 ERK-dependent phosphosites on 2,123 proteins. Respectively, 79% and 66% of those were not previously associated with ERK, significantly expanding the known ERK-dependent phosphorylation events.

The study revealed that ERK controls a complex, dynamic phosphoproteome that converges on cyclin-dependent kinase regulation and RAS homolog guanosine triphosphatase function (RHO GTPase). The researchers established that ERK1 and ERK2 share near-identical transforming and signaling outputs, and that the KRAS-regulated phosphoproteome is driven nearly completely by ERK.

This study provides the most extensive molecular picture to date of how ERK drives KRAS-dependent pancreatic cancer growth, highlighting the dominant role of the RAF-MEK-ERK signaling network in driving KRAS-mediated oncogenesis.

The IonOpticks Aurora Elite TS 15×75 C18 UHPLC column was used in this study, enabling improved phosphosite coverage and depth of analysis.



Jennifer E. Klomp, J. Nathaniel Diehl, Jeffrey A. Klomp, A. Cole Edwards, Runying Yang, Alexis J. Morales, Khalilah E. Taylor, Kristina Drizyte-Miller, Kirsten L. Bryant , Antje Schaefer , Jared L. Johnson , Emily M. Huntsman, Tomer M. Yaron, Mariaelena Pierobon, Elisa Baldelli, Alex W. Prevatte, Natalie K. Barker, Laura E. Herring, Emanuel F. Petricoin Iii, Lee M. Graves, Lewis C. Cantley, Adrienne D. Cox, Channing J. Der, Clint A. Stalnecker


Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer

Related publications & news

In a groundbreaking study by Gurung et. al, researchers expanded the repert...