Journal of Biological Chemistry
Volume 278, Issue 43, 24 October 2003, Pages 41977-41987
Journal home page for Journal of Biological Chemistry

Genes: Structure and Regulation
Megakaryoblastic Leukemia-1/2, a Transcriptional Co-activator of Serum Response Factor, Is Required for Skeletal Myogenic Differentiation*

https://doi.org/10.1074/jbc.M305679200Get rights and content
Under a Creative Commons license
open access

Serum response factor (SRF) is required for the expression of a wide variety of muscle-specific genes that are expressed upon differentiation and is thus required for both striated and smooth muscle differentiation in addition to its role in regulating growth factor-inducible genes. A heart and smooth muscle-specific SRF co-activator, myocardin, has been shown to be required for cardiac development and smooth muscle differentiation. However, no such co-factors of SRF have been identified in the skeletal myogenic differentiation program. Myocardin and the related transcription factor megakaryoblastic leukemia-1 (MKL1/MAL/MRTF-A) can strongly potentiate the activity of SRF. Here we report the cloning of the third member of the myocardin/MKL family in humans, MKL2. MKL2 binds to and activates SRF similar to myocardin and MKL1. To determine the role of these factors in skeletal myogenic differentiation we used a dominant negative MKL2 to show that the MKL family of proteins is required for skeletal myogenic differentiation. Expression of the dominant negative protein in C2C12 skeletal myoblasts blocked the differentiation-induced expression of the SRF target genes skeletal α-actin and α-myosin heavy chain and blocked differentiation of the myoblasts to myotubes in vitro. C2C12 cells express both MKL1 and MKL2, but not myocardin, implicating MKL1 and/or MKL2 in the requirement for skeletal myogenic differentiation. MKL1 was predominantly cytoplasmic in C2C12 cells, with a small amount in the nucleus, however, no movement of MKL1 to the nucleus was observed upon differentiation.

Cited by (0)

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank/EBI Data Bank with accession number(s) AY374297.

*

This work was supported by National Institutes of Health Grant CA50329 (to R. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.