Myocardin-like protein 2 regulates TGFβ signaling in embryonic stem cells and the developing vasculature

Abstract

SUMMARYThe molecular mechanisms that regulate and coordinate signaling between the extracellular matrix (ECM) and cells contributing to the developing vasculature are complex and poorly understood. Myocardin-like protein 2 (MKL2) is a transcriptional co-activator that in response to RhoA and cytoskeletal actin signals physically associates with serum response factor (SRF), activating a subset of SRF-regulated genes. We now report the discovery of a previously undescribed MKL2/TGF signaling pathway in embryonic stem (ES) cells that is required for maturation and stabilization of the embryonic vasculature.

SWATH-MS Proteomic Analysis of Oxygen-Induced Retinopathy Reveals Novel Potential Therapeutic Targets

“…Mkl2, a transcriptional coactivator, regulates conserved TGF-b signaling pathway. 63 Mice deficient for Mkl2 die at the early embryonic state, and Mkl2 À/À ECs have defects in cytoskeletal organization and cell adhesion. 63 Mkl2/TGF-b pathway is required for the maturation and stabilization of embryonic vasculature, [63][64][65] but also for the myofibroblast transformation and EMT induction.…”

“…63 Mice deficient for Mkl2 die at the early embryonic state, and Mkl2 À/À ECs have defects in cytoskeletal organization and cell adhesion. 63 Mkl2/TGF-b pathway is required for the maturation and stabilization of embryonic vasculature, [63][64][65] but also for the myofibroblast transformation and EMT induction. 66,67 The enhanced TGF-b signaling taking place in vasculature leads to the endothelial-mesenchymal transition (EndMT), a process that has many similarities with EMT.…”

SRF selectively controls tip cell invasive behavior in angiogenesis

“…We propose that, during sprouting angiogenesis, ECs engage a VEGFA-MRTF-SRF signaling pathway, the function of which is crucial for proper tip cell migration and invasion. Although Mrtfb (Mkl2) knockout mice show a vascular phenotype, it is difficult to interpret because, like SRF, MRTF-B appears to have multiple functions, including roles in heart and smooth muscle cell development (Oh et al, 2005;Li et al, 2012). Therefore, endothelial-specific analysis of MRTF-A and MRTF-B function should be addressed in the future in order to elucidate the contribution of such a pathway in sprouting angiogenesis.…”

Myocardin-Related Transcription Factor A Regulates Conversion of Progenitors to Beige Adipocytes

“…TGFβ promotes smooth muscle differentiation and coordinates the expression of SMC genes (Hautmann et al, 1997; Li et al, 2012; Sinha et al, 2004; Wang et al, 2010). TGFβ also inhibits adipocyte differentiation via its co-effector, Smad3, which complexes with C/EBPβ and represses activation of adipogenic target genes (Choy and Derynck, 2003).…”