Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer
成果类型：
Article
署名作者：
Klomp, Jennifer E.; Diehl, J. Nathaniel; Klomp, Jeffrey A.; Edwards, A. Cole; Yang, Runying; Morales, Alexis J.; Taylor, Khalilah E.; Drizyte-Miller, Kristina; Bryant, Kirsten L.; Schaefer, Antje; Johnson, Jared L.; Huntsman, Emily M.; Yaron, Tomer M.; Pierobon, Mariaelena; Baldelli, Elisa; Prevatte, Alex W.; Barker, Natalie K.; Herring, Laura E.; Petricoin III, Emanuel F.; Graves, Lee M.; Cantley, Lewis C.; Cox, Adrienne D.; Der, Channing J.; Stalnecker, Clint A.
署名单位：
University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Columbia University; George Mason University; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine
刊物名称：
SCIENCE
ISSN/ISSBN：
0036-11205
DOI：
10.1126/science.adk0850
发表日期：
2024-06-07
关键词：
differential expression
inhibition
activation
PATHWAY
kinase
identification
bioconductor
database
package
摘要：
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.