Mkl2

Summary

Gene Symbol: Mkl2
Description: MKL/myocardin-like 2
Alias: Gt4-1, MRTF-B, Mrtfb, mKIAA1243, MKL/myocardin-like protein 2, gene trap insertion site 4-1, myocardin-related transcription factor B
Species: mouse
Products:     Mkl2

Top Publications

  1. Wei K, Che N, Chen F. Myocardin-related transcription factor B is required for normal mouse vascular development and smooth muscle gene expression. Dev Dyn. 2007;236:416-25 pubmed
    ..These data support our hypothesis that MRTF-B has a unique role in regulating smooth muscle genes important for liver, yolk sac, and portal vascular development. ..
  2. Oh J, Richardson J, Olson E. Requirement of myocardin-related transcription factor-B for remodeling of branchial arch arteries and smooth muscle differentiation. Proc Natl Acad Sci U S A. 2005;102:15122-7 pubmed
    ..The phenotype of MRTF-B mutant mice is distinct from that of mice lacking myocardin, revealing unique roles for these serum response factor coactivators in the development of different subsets of smooth muscle cells in vivo. ..
  3. Costello P, Sargent M, Maurice D, Esnault C, Foster K, Anjos Afonso F, et al. MRTF-SRF signaling is required for seeding of HSC/Ps in bone marrow during development. Blood. 2015;125:1244-55 pubmed publisher
    ..Srf-null HSC/Ps exhibit substantial deficits in cytoskeletal gene expression. MRTF-SRF signaling is thus critical for expression of genes required for the response to chemokine signaling during hematopoietic development. ..
  4. Huang J, Elicker J, Bowens N, Liu X, Cheng L, Cappola T, et al. Myocardin regulates BMP10 expression and is required for heart development. J Clin Invest. 2012;122:3678-91 pubmed publisher
    ..Taken together, these data identify a heretofore undescribed myocardin/BMP10 signaling pathway that regulates cardiomyocyte proliferation and apoptosis in the embryonic heart. ..
  5. Li J, Bowens N, Cheng L, Zhu X, Chen M, Hannenhalli S, et al. Myocardin-like protein 2 regulates TGFβ signaling in embryonic stem cells and the developing vasculature. Development. 2012;139:3531-42 pubmed publisher
    ..Myocardin-like protein 2 (MKL2) is a transcriptional co-activator that in response to RhoA and cytoskeletal actin signals physically associates ..
  6. Vosseller K, Trinidad J, Chalkley R, Specht C, Thalhammer A, Lynn A, et al. O-linked N-acetylglucosamine proteomics of postsynaptic density preparations using lectin weak affinity chromatography and mass spectrometry. Mol Cell Proteomics. 2006;5:923-34 pubmed
  7. Hayashi K, Murai T, Oikawa H, Masuda T, Kimura K, Muehlich S, et al. A novel inhibitory mechanism of MRTF-A/B on the ICAM-1 gene expression in vascular endothelial cells. Sci Rep. 2015;5:10627 pubmed publisher
    ..Conversely, downregulation of MRTF-A/B alleviates this negative regulation without further translocation of NF-κB p65 into the nucleus. These results reveal the novel roles of MRTF-A/B in the homeostasis of vascular endothelium. ..
  8. Zhou J, Blue E, Hu G, Herring B. Thymine DNA glycosylase represses myocardin-induced smooth muscle cell differentiation by competing with serum response factor for myocardin binding. J Biol Chem. 2008;283:35383-92 pubmed publisher
    ..This study reveals a previously unsuspected role for the repair enzyme TDG as a repressor of smooth muscle differentiation via competing with SRF for binding to myocardin. ..
  9. Shaposhnikov D, Kuffer C, Storchova Z, Posern G. Myocardin related transcription factors are required for coordinated cell cycle progression. Cell Cycle. 2013;12:1762-72 pubmed publisher
    ..Thus, MRTFs are required for accurate cell cycle progression and maintenance of genomic stability in fibroblast cells. ..

More Information

Publications32

  1. Menendez M, Ong E, Shepherd B, Muthukumar V, Silasi Mansat R, Lupu F, et al. BRG1 (Brahma-Related Gene 1) Promotes Endothelial Mrtf Transcription to Establish Embryonic Capillary Integrity. Arterioscler Thromb Vasc Biol. 2017;37:1674-1682 pubmed publisher
    ..Instead, we found that BRG1 binds to the promoters of the SRF cofactors Mrtfa and Mrtfb (myocardin-related transcription factors A and B) in endothelial cells, and these genes are downregulated in <..
  2. Trembley M, Velasquez L, de Mesy Bentley K, Small E. Myocardin-related transcription factors control the motility of epicardium-derived cells and the maturation of coronary vessels. Development. 2015;142:21-30 pubmed publisher
    ..Conditional ablation of Mrtfa and Mrtfb specifically in the epicardium disrupts cell migration and leads to sub-epicardial hemorrhage, partially stemming ..
  3. Medjkane S, Perez Sanchez C, Gaggioli C, Sahai E, Treisman R. Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis. Nat Cell Biol. 2009;11:257-68 pubmed publisher
    ..Actin-based cell behaviour and experimental metastasis thus require Rho-dependent nuclear signalling through the MRTF-SRF network. ..
  4. Yoshio T, Morita T, Tsujii M, Hayashi N, Sobue K. MRTF-A/B suppress the oncogenic properties of v-ras- and v-src-mediated transformants. Carcinogenesis. 2010;31:1185-93 pubmed publisher
    ..In vivo, CA-MRTF-A expression suppressed tumor formation and reduced liver metastases. Therefore, we concluded that MRTF-A/B are potent repressors of cancer progression and metastasis and may be good targets for cancer therapy. ..
  5. Xie W, Li Z, Shi N, Guo X, Tang J, Ju W, et al. Smad2 and myocardin-related transcription factor B cooperatively regulate vascular smooth muscle differentiation from neural crest cells. Circ Res. 2013;113:e76-86 pubmed publisher
    ..Vascular smooth muscle cell (VSMC) differentiation from neural crest cells (NCCs) is critical for cardiovascular development, but the mechanisms remain largely unknown...
  6. Xie L. MKL1/2 and ELK4 co-regulate distinct serum response factor (SRF) transcription programs in macrophages. BMC Genomics. 2014;15:301 pubmed publisher
    ..Together, these findings indicate that SRF, along with its two cofactors, are important players in both cellular homeostasis and stress responses in macrophages. ..
  7. Staus D, Weise Cross L, Mangum K, Medlin M, Mangiante L, Taylor J, et al. Nuclear RhoA signaling regulates MRTF-dependent SMC-specific transcription. Am J Physiol Heart Circ Physiol. 2014;307:H379-90 pubmed publisher
    ..Taken together, these data support the emerging idea that RhoA-dependent nuclear actin polymerization has important effects on transcription and nuclear structure. ..
  8. Lockman K, Taylor J, Mack C. The histone demethylase, Jmjd1a, interacts with the myocardin factors to regulate SMC differentiation marker gene expression. Circ Res. 2007;101:e115-23 pubmed
  9. Cenik B, Liu N, Chen B, Bezprozvannaya S, Olson E, Bassel Duby R. Myocardin-related transcription factors are required for skeletal muscle development. Development. 2016;143:2853-61 pubmed publisher
    ..Our findings reveal a central role for MRTFs in sarcomere formation during skeletal muscle development and point to the potential involvement of these transcriptional co-activators in skeletal myopathies. ..
  10. Kuwahara K, Barrientos T, Pipes G, Li S, Olson E. Muscle-specific signaling mechanism that links actin dynamics to serum response factor. Mol Cell Biol. 2005;25:3173-81 pubmed
  11. Weinl C, Riehle H, Park D, Stritt C, Beck S, Huber G, et al. Endothelial SRF/MRTF ablation causes vascular disease phenotypes in murine retinae. J Clin Invest. 2013;123:2193-206 pubmed publisher
  12. Li J, Zhu X, Chen M, Cheng L, Zhou D, Lu M, et al. Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development. Proc Natl Acad Sci U S A. 2005;102:8916-21 pubmed
  13. Skarnes W, Auerbach B, Joyner A. A gene trap approach in mouse embryonic stem cells: the lacZ reported is activated by splicing, reflects endogenous gene expression, and is mutagenic in mice. Genes Dev. 1992;6:903-18 pubmed
    ..This work demonstrates the capacity of the gene trap vector to generate lacZ fusion transcripts, to accurately report endogenous gene expression, and to mutate the endogenous gene at the site of integration. ..
  14. Wang D, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, et al. Potentiation of serum response factor activity by a family of myocardin-related transcription factors. Proc Natl Acad Sci U S A. 2002;99:14855-60 pubmed
    ..Myocardin and MRTFs comprise a previously uncharacterized family of SRF cofactors with the potential to modulate SRF target genes in a wide range of tissues. ..
  15. SMITH E, Thon J, Devine M, Lin S, Schulz V, Guo Y, et al. MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation. Blood. 2012;120:2317-29 pubmed publisher
    ..We show that MKL2, a homologue of MKL1, is expressed in megakaryocytes and plays a role in megakaryocyte maturation...
  16. Mokalled M, Johnson A, Kim Y, Oh J, Olson E. Myocardin-related transcription factors regulate the Cdk5/Pctaire1 kinase cascade to control neurite outgrowth, neuronal migration and brain development. Development. 2010;137:2365-74 pubmed publisher
    ..Here, we show that MRTF-A (Mkl1) and MRTF-B (Mkl2) redundantly control neuronal migration and neurite outgrowth during mouse brain development...
  17. Morita T, Mayanagi T, Sobue K. Reorganization of the actin cytoskeleton via transcriptional regulation of cytoskeletal/focal adhesion genes by myocardin-related transcription factors (MRTFs/MAL/MKLs). Exp Cell Res. 2007;313:3432-45 pubmed
    ..These results indicate that MRTF-A/B act as pivotal mediators of stress fiber and focal adhesion formation via the transcriptional regulation of a subset of cytoskeletal/focal adhesion genes. ..
  18. Weinl C, Castaneda Vega S, Riehle H, Stritt C, Calaminus C, Wolburg H, et al. Endothelial depletion of murine SRF/MRTF provokes intracerebral hemorrhagic stroke. Proc Natl Acad Sci U S A. 2015;112:9914-9 pubmed publisher
    ..We hypothesize that impairments in SRF/MRTF activity contribute to human SVD pathology. ..
  19. Mokalled M, Carroll K, Cenik B, Chen B, Liu N, Olson E, et al. Myocardin-related transcription factors are required for cardiac development and function. Dev Biol. 2015;406:109-16 pubmed publisher
    ..Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. ..
  20. Parmacek M. Myocardin-related transcription factors: critical coactivators regulating cardiovascular development and adaptation. Circ Res. 2007;100:633-44 pubmed
    ..Myocardin-related transcription factors (MRTFs), including myocardin, MRTF-A/MKL1/MAL, and MRTF-B/MKL2, comprise a family of related transcriptional coactivators that physically associate with the MADS box ..
  21. Goss A, Tian Y, Cheng L, Yang J, Zhou D, Cohen E, et al. Wnt2 signaling is necessary and sufficient to activate the airway smooth muscle program in the lung by regulating myocardin/Mrtf-B and Fgf10 expression. Dev Biol. 2011;356:541-52 pubmed publisher
    ..These studies place Wnt2 high in a hierarchy of signaling molecules that promote the earliest aspects of lung airway smooth muscle development. ..
  22. French W, Creemers E, Tallquist M. Platelet-derived growth factor receptors direct vascular development independent of vascular smooth muscle cell function. Mol Cell Biol. 2008;28:5646-57 pubmed publisher
    ..Together, these data demonstrate that PDGF receptors cooperate in the yolk sac mesothelium to direct blood vessel maturation and suggest that these effects are independent of their role in VSMC development...
  23. Moritani M, Togawa K, Yaguchi H, Fujita Y, Yamaguchi Y, Inoue H, et al. Identification of diabetes susceptibility loci in db mice by combined quantitative trait loci analysis and haplotype mapping. Genomics. 2006;88:719-730 pubmed publisher
    ..6 Mb by excluding shared haplotype regions and identified 11 nonsynonymous single-nucleotide polymorphisms in six candidate genes. ..