TY - JOUR
T1 - Characterization of leukemia-associated Rho guanine nucleotide exchange factor (LARG) expression during murine development
AU - Becknell, Brian
AU - Shen, Tiansheng
AU - Maghraby, Eman
AU - Taya, Shinichiro
AU - Kaibuchi, Kozo
AU - Caligiuri, Michael A.
AU - Marcucci, Guido
N1 - Funding 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
PY - 2003/12
Y1 - 2003/12
N2 - 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.
AB - 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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U2 - 10.1007/s00441-003-0802-5
DO - 10.1007/s00441-003-0802-5
M3 - Article
C2 - 14513355
AN - SCOPUS:0345117225
SN - 0302-766X
VL - 314
SP - 361
EP - 366
JO - Cell and Tissue Research
JF - Cell and Tissue Research
IS - 3
ER -