ArticleMolecular and cellular biology2003
MEK kinase 2 and the adaptor protein Lad regulate extracellular signal-regulated kinase 5 activation by epidermal growth factor via Src.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Meta-analysis of gene expression signatures defining the epithelial to mesenchymal transition during cancer progression.PloS one · 2012Pooled it
- A pooled Cell Painting CRISPR screening platform enables de novo inference of gene function by self-supervised deep learning.Nature communications · 2025Article
- Review
- Article
- The Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Pathway in Osteoblasts.Journal of bone metabolism · 2022Article
- Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition in Cancer.International journal of molecular sciences · 2019Review
- miR-302a inhibits human HepG2 and SMMC-7721 cells proliferation and promotes apoptosis by targeting MAP3K2 and PBX3.Scientific reports · 2019Article
- MAPK and PI3K signaling: At the crossroads of neural crest development.Developmental biology · 2018Review
- KRAS Suppression-Induced Degradation of MYC Is Antagonized by a MEK5-ERK5 Compensatory Mechanism.Cancer cell · 2018Article
- Kir2.1 Interaction with Stk38 Promotes Invasion and Metastasis of Human Gastric Cancer by Enhancing MEKK2-MEK1/2-ERK1/2 Signaling.Cancer research · 2018Article
- Tumor-derived exosomes antagonize innate antiviral immunity.Nature immunology · 2018Article
- MEKK2 mediates an alternative β-catenin pathway that promotes bone formation.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Extracellular signal-regulated kinase 5 promotes acute cellular and systemic inflammation.Science signaling · 2015Article
- MEKK2 regulates paxillin ubiquitylation and localization in MDA-MB 231 breast cancer cells.The Biochemical journal · 2014Article
- Cancer biology: Enzyme meets a surprise target.Nature · 2014Article
- Article
- Overexpression of MEKK2 is associated with colorectal carcinogenesis.Oncology letters · 2013Article
- MEKK2 kinase association with 14-3-3 protein regulates activation of c-Jun N-terminal kinase.The Journal of biological chemistry · 2013Article
- Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Lad is an SH2 domain-containing adaptor protein that binds MEK kinase 2 (MEKK2), a mitogen-activated protein kinase (MAPK) kinase kinase for the extracellular signal-regulated kinase 5 (ERK5) and JNK pathways. Lad and MEKK2 are in a complex in resting cells. Antisense knockdown of Lad expression and targeted gene disruption of MEKK2 expression results in loss of epidermal growth factor (EGF) and stress stimuli-induced activation of ERK5. Activation of MEKK2 and the ERK5 pathway by EGF and stress stimuli is dependent on Src kinase activity. The Lad-binding motif is encoded within amino acids 228 to 282 in the N terminus of MEKK2, and expression of this motif blocks Lad-MEKK2 interaction, resulting in inhibition of Src-dependent activation of MEKK2 and ERK5. JNK activation by EGF is similarly inhibited by loss of Lad or MEKK2 expression and by blocking the interaction of MEKK2 and Lad. Our studies demonstrate that Src kinase activity is required for ERK5 activation in response to EGF, MEKK2 expression is required for ERK5 activation by Src, Lad and MEKK2 association is required for Src activation of ERK5, and EGF and Src stimulation of ERK5-regulated MEF2-dependent promoter activity requires a functional Lad-MEKK2 signaling complex.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.