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A human homolog of mouse Lbh gene, hLBH, expresses in heart and activates SRE and AP-1 mediated MAPK signaling pathway

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Abstract

It has been reported that mouse Lbh (limb-bud and heart) can regulate cardiac gene expression by modulating the combinatorial activities of key cardiac transcription factors, as well as their individual functions in cardiogenesis. Here we report the cloning and characterization of the human homolog of mouse Lbh gene, hLBH, from a human embryonic heart cDNA library. The cDNA of hLBH is 2927 bp long, encoding a protein product of 105 amino acids. The protein is highly conserved in evolution across different species from zebra fish, to mouse, to human. Northern blot analysis indicates that a 2.9 kb transcript specific for hLBH is most abundantly expressed in both embryonic and adult heart tissue. In COS-7 cells, hLBH proteins are localized to both the nucleus and the cytoplasm. hLBH is a transcription activator when fused to Gal-4 DNA-binding domain. Deletion analysis indicates that both the N-terminal containing proline-dependent serine/threonine kinase group and the C-terminal containing ERK D-domain motif are required for transcriptional activation. Overexpression of hLBH in COS-7 cells activates the transcriptional activities of activator protein-1 (AP-1) and serum response element (SRE). These results suggest that hLBH proteins may act as a transcriptional activator in mitogen-activated protein kinase signaling pathway to mediate cellular functions.

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Abbreviations

DMEM:

Dulbecco’s Modified Eagle Medium

DAPI:

4′,6′-diamidino-2-phenylindole hydrochloride

MAPK:

Mitogen-activated protein kinase

MAPKK, MKK or MEK:

MAPK kinase

MAPKKK or MEKK:

A MAPKK kinase or MEK kinase

SRE:

Serum response element

AP-1:

Activation protein 1

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Acknowledgments

We are grateful to all members of the Center for Heart Development, College of Life Sciences in Hunan Normal University for their excellent technical assistance and encouragement. This study was supported in part by the National Natural Science Foundation of China (No. 90508004, 30470867, 30570934, 30571048), PCSIRT of Education Ministry of China (IRT0445), National Basic Research Program of China (2005CB522505), the Foundation of Hunan Province (No. 05FJ2007, 06JJ4120), and Scientific and Research Fund of Hunan Provincial Education Department (04C327).

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Correspondence to Mingyao Liu or Xiushan Wu.

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The authors Jianping Ai and Yuequn Wang have contributed equally to the work.

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Ai, J., Wang, Y., Tan, K. et al. A human homolog of mouse Lbh gene, hLBH, expresses in heart and activates SRE and AP-1 mediated MAPK signaling pathway. Mol Biol Rep 35, 179–187 (2008). https://doi.org/10.1007/s11033-007-9068-4

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