ArticleJournal of the American Heart Association2015
Myristoylated Alanine-Rich Protein Kinase Substrate (MARCKS) Regulates Small GTPase Rac1 and Cdc42 Activity and Is a Critical Mediator of Vascular Smooth Muscle Cell Migration in Intimal Hyperplasia Formation.
Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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
27 citing papers in PubMed, 39 citations in OpenAlex.
- TEAD-independent mechanisms of YAP function in cardiomyocyte cell cycle reentry.Life science alliance · 2026Article
- Neutrophil elastase promotes mucin secretion in airway epithelial cells through the MARCKS/ACK1/cortactin pathway.Central-European journal of immunology · 2025Article
- Z-Ligustilide: A Potential Therapeutic Agent for Atherosclerosis Complicating Cerebrovascular Disease.Biomolecules · 2024Review
- Role for the PIPJournal of cell communication and signaling · 2024Review
- Advancements in Omics and Breakthrough Gene Therapies: A Glimpse into the Future of Peripheral Artery Disease.Annals of vascular surgery · 2024Review
- The Cdc42/Rac1 pathway: a molecular mechanism behind iron-deficiency-driven aortic medial degeneration.American journal of translational research · 2024Article
- Article
- Article
- The myristoylated alanine-rich C-kinase substrates (MARCKS): A membrane-anchored mediator of the cell function.Autoimmunity reviews · 2021Review
- Weighted Gene Co-Expression Network Analysis Reveals Key Genes and Potential Drugs in Abdominal Aortic Aneurysm.Biomedicines · 2021Article
- Pathophysiological roles of myristoylated alanine-rich C-kinase substrate (MARCKS) in hematological malignancies.Biomarker research · 2021Review
- MARCKSL1 promotes the proliferation, migration and invasion of lung adenocarcinoma cells.Oncology letters · 2020Article
- The myristoylated alanine-rich C kinase substrate differentially regulates kinase interacting with stathmin in vascular smooth muscle and endothelial cells and potentiates intimal hyperplasia formation.Journal of vascular surgery · 2019Article
- Myristoylated alanine-rich C-kinase substrate effector domain phosphorylation regulates the growth and radiation sensitization of glioblastoma.International journal of oncology · 2019Article
- Small GTPases and Their Role in Vascular Disease.International journal of molecular sciences · 2019Review
- MARCKS and Lung Disease.American journal of respiratory cell and molecular biology · 2019Review
- MARCKS regulates neuritogenesis and interacts with a CDC42 signaling network.Scientific reports · 2018Article
- Carnosic acid protects mice from high-fat diet-induced NAFLD by regulating MARCKS.International journal of molecular medicine · 2018Article
- MARCKS and MARCKS-like proteins in development and regeneration.Journal of biomedical science · 2018Review
- 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
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundTranscription of the myristoylated alanine-rich C kinase substrate (MARCKS) is upregulated in animal models of intimal hyperplasia. MARCKS knockdown inhibits vascular smooth muscle cell (VSMC) migration in vitro; however, the mechanism is as yet unknown. We sought to elucidate the mechanism of MARCKS-mediated motility and determine whether MARCKS knockdown reduces intimal hyperplasia formation in vivo. METHODS AND
resultsMARCKS knockdown blocked platelet-derived growth factor (PDGF)-induced translocation of cortactin to the cell cortex, impaired both lamellipodia and filopodia formation, and attenuated motility of human coronary artery smooth muscle cells (CASMCs). Activation of the small GTPases, Rac1 and Cdc42, was prevented by MARCKS knockdown. Phosphorylation of MARCKS resulted in a transient shift of MARCKS from the plasma membrane to the cytosol. MARCKS knockdown significantly decreased membrane-associated phosphatidylinositol 4,5-bisphosphate (PIP2) levels. Cotransfection with an intact, unphosphorylated MARCKS, which has a high binding affinity for PIP2, restored membrane-associated PIP2 levels and was indispensable for activation of Rac1 and Cdc42 and, ultimately, VSMC migration. Overexpression of MARCKS in differentiated VSMCs increased membrane PIP2 abundance, Rac1 and Cdc42 activity, and cell motility. MARCKS protein was upregulated early in the development of intimal hyperplasia in the murine carotid ligation model. Decreased MARKCS expression, but not total knockdown, attenuated intimal hyperplasia formation.
conclusionsMARCKS upregulation increases VSMC motility by activation of Rac1 and Cdc42. These effects are mediated by MARCKS sequestering PIP2 at the plasma membrane. This study delineates a novel mechanism for MARCKS-mediated VSMC migration and supports the rational for MARCKS knockdown to prevent intimal hyperplasia.
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.