Summary of 257-Kubota-ERKActivity

SSBD:database
SSBD:database URL
Title
Time-lapse confocal images of ERK1-EGFP for MEK1-WT or MEK1-mutations after EGF stimulation.
Description
-
Relase date
2023-03-22
Updated date
-
License
CC BY
Kind
Image data based on Experiment
Number of Datasets
3 ( Image datasets: 3, Quantitative data datasets: 0 )
Size of Datasets
141.6 MB ( Image datasets: 141.6 MB, Quantitative data datasets: 0 bytes )

Organism(s)
Homo sapiens
Cell lines(s)
HEK293
Protein name(s)
ERK1, MEK1
Protein tag(s)
EGFP

Datatype
-
Molecular Function (MF)
MAP kinase activity
Biological Process (BP)
MAPK cascade
Cellular Component (CC)
Biological Imaging Method
time lapse microscopy
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
-

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


Dataset List of 257-Kubota-ERKActivity

#
Dataset ID
Kind
Size
4D View
SSBD:OMERO
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# 10494
Dataset Kind Image data
Dataset Size 40.5 MB
4D view
SSBD:OMERO
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# 10495
Dataset Kind Image data
Dataset Size 40.5 MB
4D view
SSBD:OMERO
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# 10496
Dataset Kind Image data
Dataset Size 60.6 MB
4D view
SSBD:OMERO
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