ArticleMolecular and cellular biology2008
Serum-induced phosphorylation of the serum response factor coactivator MKL1 by the extracellular signal-regulated kinase 1/2 pathway inhibits its nuclear localization.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 106 citations in OpenAlex.
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- Re-evaluating Gα protein-response element specificity in GPCR signaling.Communications biology · 2026Article
- Characterizing the Effects of Protein Glycosylation Perturbation on Phosphorylation Signaling.bioRxiv : the preprint server for biology · 2025Article
- Identification of novel inhibitors of the transcriptional coactivator MRTF-A for HCC therapy.Molecular therapy. Oncology · 2024Article
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- Transforming Growth Factor-β Receptor-Mediated, p38 Mitogen-Activated Protein Kinase-Dependent Signaling Drives Enhanced Myofibroblast Differentiation during Skin Wound Healing in Mice Lacking Hyaluronan Synthases 1 and 3.The American journal of pathology · 2022Article
- Relieving DYRK1A repression of MKL1 confers an adult-like phenotype to human infantile megakaryocytes.The Journal of clinical investigation · 2022Article
- Myocardin-related transcription factor's interaction with serum-response factor is critical for outgrowth initiation, progression, and metastatic colonization of breast cancer cells.FASEB bioAdvances · 2022Article
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- Vascular smooth muscle cells in intimal hyperplasia, an update.Frontiers in physiology · 2022Review
- Pharmacological regulation of tissue fibrosis by targeting the mechanical contraction of myofibroblasts.Fundamental research · 2022Article
- MRTF: Basic Biology and Role in Kidney Disease.International journal of molecular sciences · 2021Review
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- RhoA: a dubious molecule in cardiac pathophysiology.Journal of biomedical science · 2021Review
- Journey to the Center of the Cell: Cytoplasmic and Nuclear Actin in Immune Cell Functions.Frontiers in cell and developmental biology · 2021Review
- MRTF-A regulates CaJournal of biosciences · 2021Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Megakaryoblastic leukemia 1 (MKL1) is a myocardin-related coactivator of the serum response factor (SRF) transcription factor, which has an integral role in differentiation, migration, and proliferation. Serum induces RhoA-dependent translocation of MKL1 from the cytoplasm to the nucleus and also causes a rapid increase in MKL1 phosphorylation. We have mapped a serum-inducible phosphorylation site and found, surprisingly, that its mutation causes constitutive localization to the nucleus, suggesting that phosphorylation of MKL1 inhibits its serum-induced nuclear localization. The key site, serine 454, resembles a mitogen-activated protein kinase phosphorylation site, and its modification was blocked by the MEK1 inhibitor U0126, implying that extracellular signal-regulated kinase 1/2 (ERK1/2) is the serum-inducible kinase that phosphorylates MKL1. Previous results indicated that G-actin binding to MKL1 promotes its nuclear export, and we found that MKL1 phosphorylation is required for its binding to actin, explaining its effect on localization. We propose a model in which serum induction initially stimulates MKL1 nuclear localization due to a decrease in G-actin levels, but MKL1 is then downregulated by nuclear export due to ERK1/2 phosphorylation.
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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.