Detail of Fig4cd_MEK1-K57N_after_EGF_stimulation



Project
Title
Time-lapse confocal images of ERK1-EGFP for MEK1-K57N after EGF stimulation.
Description
Time-lapse confocal images of ERK1-EGFP for MEK1-K57N after EGF stimulation.
Release, Updated
2023-03-22
License
CC BY
Kind
Image data
File Formats
.TIF
Data size
60.6 MB

Organism
Homo sapiens ( NCBI:txid9606 )
Strain(s)
-
Cell Line
HEK293 ( CLO_0001230 )
Protein names
ERK1, MEK1
Protein tags
EGFP

Datatype
-
Molecular Function (MF)
MAP kinase activity ( GO:0004707 )
Biological Process (BP)
MAPK cascade ( GO:0000165 )
Cellular Component (CC)
Biological Imaging Method
time lapse microscopy ( Fbbi:00000249 )
X scale
0.26 micrometer/pixel
Y scale
0.26 micrometer/pixel
Z scale
-
T scale
1.5 minutes of time interval

Image Acquisition
Experiment type
-
Microscope type
-
Acquisition mode
-
Contrast method
-
Microscope model
-
Detector model
-
Objective model
-
Filter set
-

Summary of Methods
See details in Kubota Y, et. al. (2022) Nat Commun. 2022 Jul 13;13(1):4063.
Related paper(s)

Yuji Kubota, Yuko Fujioka, Ashwini Patil, Yusuke Takagi, Daisuke Matsubara, Masatomi Iijima, Isao Momose, Ryosuke Naka, Kenta Nakai, Nobuo N Noda, Mutsuhiro Takekawa (2022) Qualitative differences in disease-associated MEK mutants reveal molecular signatures and aberrant signaling-crosstalk in cancer., Nature communications, Volume 13, Number 1, pp. 4063

Published in 2022 Jul 13 (Electronic publication in July 13, 2022, midnight )

(Abstract) Point-mutations of MEK1, a central component of ERK signaling, are present in cancer and RASopathies, but their precise biological effects remain obscure. Here, we report a mutant MEK1 structure that uncovers the mechanisms underlying abnormal activities of cancer- and RASopathy-associated MEK1 mutants. These two classes of MEK1 mutations differentially impact on spatiotemporal dynamics of ERK signaling, cellular transcriptional programs, gene expression profiles, and consequent biological outcomes. By making use of such distinct characteristics of the MEK1 mutants, we identified cancer- and RASopathy-signature genes that may serve as diagnostic markers or therapeutic targets for these diseases. In particular, two AKT-inhibitor molecules, PHLDA1 and 2, are simultaneously upregulated by oncogenic ERK signaling, and mediate cancer-specific ERK-AKT crosstalk. The combined expression of PHLDA1/2 is critical to confer resistance to ERK pathway-targeted therapeutics on cancer cells. Finally, we propose a therapeutic strategy to overcome this drug resistance. Our data provide vital insights into the etiology, diagnosis, and therapeutic strategy of cancers and RASopathies.
(MeSH Terms)

Contact
Mutsuhiro Takekawa , The University of Tokyo , Institute of Medical Science , Division of Cell Signaling and Molecular Medicine
Contributors

OMERO Dataset
OMERO Project
Source