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Roles of bone morphogenetic protein type I receptors and Smad proteins in osteoblast and chondroblast differentiation 总被引:18,自引:0,他引:18
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Fujii M Takeda K Imamura T Aoki H Sampath TK Enomoto S Kawabata M Kato M Ichijo H Miyazono K 《Molecular biology of the cell》1999,10(11):3801-3813
The biological effects of type I serine/threonine kinase receptors and Smad proteins were examined using an adenovirus-based vector system. Constitutively active forms of bone morphogenetic protein (BMP) type I receptors (BMPR-IA and BMPR-IB; BMPR-I group) and those of activin receptor-like kinase (ALK)-1 and ALK-2 (ALK-1 group) induced alkaline phosphatase activity in C2C12 cells. Receptor-regulated Smads (R-Smads) that act in the BMP pathways, such as Smad1 and Smad5, also induced the alkaline phosphatase activity in C2C12 cells. BMP-6 dramatically enhanced alkaline phosphatase activity induced by Smad1 or Smad5, probably because of the nuclear translocation of R-Smads triggered by the ligand. Inhibitory Smads, i.e., Smad6 and Smad7, repressed the alkaline phosphatase activity induced by BMP-6 or the type I receptors. Chondrogenic differentiation of ATDC5 cells was induced by the receptors of the BMPR-I group but not by those of the ALK-1 group. However, kinase-inactive forms of the receptors of the ALK-1 and BMPR-I groups blocked chondrogenic differentiation. Although R-Smads failed to induce cartilage nodule formation, inhibitory Smads blocked it. Osteoblast differentiation induced by BMPs is thus mediated mainly via the Smad-signaling pathway, whereas chondrogenic differentiation may be transmitted by Smad-dependent and independent pathways. 相似文献
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Pan D Estévez-Salmerón LD Stroschein SL Zhu X He J Zhou S Luo K 《The Journal of biological chemistry》2005,280(16):15992-16001
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Smads as transcriptional co-modulators 总被引:46,自引:0,他引:46
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Direct binding of Smad1 and Smad4 to two distinct motifs mediates bone morphogenetic protein-specific transcriptional activation of Id1 gene. 总被引:11,自引:0,他引:11
Teresa López-Rovira Elisabet Chalaux Joan Massagué Jose Luis Rosa Francesc Ventura 《The Journal of biological chemistry》2002,277(5):3176-3185
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Tylzanowski P Verschueren K Huylebroeck D Luyten FP 《The Journal of biological chemistry》2001,276(43):40001-40007
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Smad6 is a Smad1/5-induced smad inhibitor. Characterization of bone morphogenetic protein-responsive element in the mouse Smad6 promoter 总被引:7,自引:0,他引:7
Ishida W Hamamoto T Kusanagi K Yagi K Kawabata M Takehara K Sampath TK Kato M Miyazono K 《The Journal of biological chemistry》2000,275(9):6075-6079
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Tasima Haque Manuela Mandu-Hrit Frank Rauch Dominique Lauzier Maryam Tabrizian Reggie C Hamdy 《The journal of histochemistry and cytochemistry》2006,54(4):407-415
In this study we investigated the expression of bone morphogenetic protein (BMP)-signaling Smads in distraction osteogenesis (DO). Osteotomy of the right tibia was performed in 14 skeletally mature white New Zealand male rabbits. Lengthening was started 1 week later at a rate of 0.5 mm/12 hr and was maintained for 3 weeks. Expression of Smad proteins 1, 4, 5, 6, 7, and 8 and Smad ubiquitin regulatory factors (Smurfs) 1 and 2 was evaluated in the distracted zone using immunohistochemistry. Expression of receptor-regulated Smads (R-Smads) 1, 5, and 8 showed a significant increase during the distraction phase, followed by a gradual decrease during the consolidation phase. Smad 4 showed significant expression during both distraction and the beginning of the consolidation phase. Smad 6 and Smad 7 were highly expressed during the consolidation phase. Staining for both Smurfs 1 and 2 was maximal at the end of the distraction period. Staining for all proteins was most intense in chondrocyte and fibroblast-like cells. Expression pattern of R-Smads correlated with our previously reported expression pattern of BMPs 2, 4, and 7 and their receptors. These results therefore suggest a role for the whole BMP signaling pathway including the Smad proteins in DO. 相似文献