KMID : 0578320100300040335
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Molecules and Cells 2010 Volume.30 No. 4 p.335 ~ p.340
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Leukocyte Common Antigen-Related (LAR) Tyro-sine Phosphatase Positively Regulates Osteoblast Differentiation by Modulating Extracellular Signal-Regulated Kinase (ERK) Activation
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Kim Won-Kon
Bae Kwang-Hee Choi Hye-Ryung Kim Do-Hyung Choi Kwang-Soo Cho Yee-Sook Kim Hee-Dai Park Sung-Goo Park Byoung-Chul Ko Yong Lee Sang-Chul
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Abstract
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Protein tyrosine phosphatases (PTPs) are pivotal regula-tors of key cellular functions, including cell growth, diffe-rentiation, and adhesion. Previously, we reported that leukocyte common antigen-related (LAR) tyrosine phosphatase promotes osteoblast differentiation in MC3T3-E1 preosteoblast cells. In the present study, the mechanism of the regulatory action of LAR on osteoblast differentiation was investigated. The mineralization of extracellular matrix and calcium accumulation in MC3T3-E1 cells were markedly enhanced by LAR overexpression, and these effects were further increased by treatment with an MEK inhibitor. In addition, LAR overexpression dramatically reduced extracellular signal-regulated kinase (Erk) activation during osteoblast differentiation. In contrast, a marginal effect of the inactive LAR mutant on Erk activation was detected. Expression of osteoblast-related genes such as ALP, BSP, DLX5, OCN, and RUNX2, was increased by LAR overex-pression during osteoblast differentiation. On the basis of these results, we propose that LAR functions as a positive regulator of osteoblast differentiation by modulating ERK activation. Therefore, LAR phosphatase could be used as a novel regulatory target protein in many bone-associated diseases, including osteoporosis.
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KEYWORD
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differentiation, ERK, LAR tyrosine phosphatase, osteoblast
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