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Characterization of leukemia-associated Rho guanine nucleotide exchange factor (LARG) expression during murine development

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Abstract

LARG (leukemia-associated Rho guanine nucleotide exchange factor, ARHGEF12) was originally identified as a fusion partner of the MLL gene at 11q23 in human acute myeloid leukemia. We have previously demonstrated that the LARG protein activates RhoA, a member of the Rho family of small GTPases, by catalyzing the exchange of GTP for GDP. Experiments in Drosophila melanogaster have implicated RhoA and its regulators in a spectrum of developmental processes—including gastrulation, neurite outgrowth, and epidermal morphogenesis; however, the role of these genes during mammalian development is incompletely understood. Herein, we investigate the expression of the murine LARG homologue during embryogenesis and in adult animals, by a combination of mRNA in situ hybridization and immunohistochemical detection of the LARG protein. We observe that LARG transcript and protein are undetectable prior to embryonic day 14. Beginning at this stage, LARG is expressed in the skin, intestinal epithelium, and smooth muscle layers of the intestine, bronchi, and vasculature. This specific distribution is maintained at later stages of development and into adulthood. Finally, we demonstrate colocalization of the LARG protein with the insulin-like growth factor-I (IGF-1) receptor, suggesting a potential physiologic role for LARG as an activator of RhoA in response to IGF-1.

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Acknowledgements

We are grateful to Dr. Ning Quan for his valuable help and Dr. Lizhao Wu for expert embryo dissections.

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Authors and Affiliations

  1. Integrated Biomedical Science Graduate Program, College of Medicine and Public Health, The Ohio State University, OH 43210, USA

    Brian Becknell

  2. Division of Hematology-Oncology, Department of Internal Medicine, College of Medicine and Public Health and The Comprehensive Cancer Center, The Ohio State University, OH 43210, USA

    Tiansheng Shen & Guido Marcucci

  3. Department of Clinical Pathology, Assiut University, Egypt

    Eman Maghraby

  4. Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Japan

    Shinichiro Taya & Kozo Kaibuchi

  5. Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine and Public Health and The Comprehensive Cancer Center, The Ohio State University, OH 43210, USA

    Michael A. Caligiuri & Guido Marcucci

  6. The Ohio State University, 458A Starling-Loving Hall, 320 West 10th Avenue Columbus, OH 43210, USA

    Guido Marcucci

Authors
  1. Brian Becknell
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  2. Tiansheng Shen
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  3. Eman Maghraby
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  4. Shinichiro Taya
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  5. Kozo Kaibuchi
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  6. Michael A. Caligiuri
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  7. Guido Marcucci
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Corresponding author

Correspondence to Guido Marcucci.

Additional information

The first two authors contributed equally to this work. The study was supported by grants PA-CA16058 and KO8 CA90469 from the National Cancer Institute, Bethesda, MD

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Becknell, B., Shen, T., Maghraby, E. et al. Characterization of leukemia-associated Rho guanine nucleotide exchange factor (LARG) expression during murine development. Cell Tissue Res 314, 361–366 (2003). https://doi.org/10.1007/s00441-003-0802-5

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  • DOI: https://doi.org/10.1007/s00441-003-0802-5

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