共查询到20条相似文献,搜索用时 31 毫秒
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Divergence and convergence of TGF-beta/BMP signaling 总被引:41,自引:0,他引:41
The transforming growth factor-beta (TGF-beta) superfamily includes more than 30 members which have a broad array of biological activities. TGF-beta superfamily ligands bind to type II and type I serine/threonine kinase receptors and transduce signals via Smad proteins. Receptor-regulated Smads (R-Smads) can be classified into two subclasses, i.e. those activated by activin and TGF-beta signaling pathways (AR-Smads), and those activated by bone morphogenetic protein (BMP) pathways (BR-Smads). The numbers of type II and type I receptors and Smad proteins are limited. Thus, signaling of the TGF-beta superfamily converges at the receptor and Smad levels. In the intracellular signaling pathways, Smads interact with various partner proteins and thereby exhibit a wide variety of biological activities. Moreover, signaling by Smads is modulated by various other signaling pathways allowing TGF-beta superfamily ligands to elicit diverse effects on target cells. Perturbations of the TGF-beta/BMP signaling pathways result in various clinical disorders including cancers, vascular diseases, and bone disorders. 相似文献
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J W Wu M Hu J Chai J Seoane M Huse C Li D J Rigotti S Kyin T W Muir R Fairman J Massagué Y Shi 《Molecular cell》2001,8(6):1277-1289
Ligand-induced phosphorylation of the receptor-regulated Smads (R-Smads) is essential in the receptor Ser/Thr kinase-mediated TGF-beta signaling. The crystal structure of a phosphorylated Smad2, at 1.8 A resolution, reveals the formation of a homotrimer mediated by the C-terminal phosphoserine (pSer) residues. The pSer binding surface on the MH2 domain, frequently targeted for inactivation in cancers, is highly conserved among the Co- and R-Smads. This finding, together with mutagenesis data, pinpoints a functional interface between Smad2 and Smad4. In addition, the pSer binding surface on the MH2 domain coincides with the surface on R-Smads that is required for docking interactions with the serine-phosphorylated receptor kinases. These observations define a bifunctional role for the MH2 domain as a pSer-X-pSer binding module in receptor Ser/Thr kinase signaling pathways. 相似文献
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TGF-beta signaling by Smad proteins 总被引:26,自引:0,他引:26
Miyazono K 《Cytokine & growth factor reviews》2000,11(1-2):15-22
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The Smads 总被引:8,自引:0,他引:8
Hill CS 《The international journal of biochemistry & cell biology》1999,31(11):1249-1254
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How the Smads regulate transcription 总被引:4,自引:0,他引:4
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Nuclear factor YY1 inhibits transforming growth factor beta- and bone morphogenetic protein-induced cell differentiation 总被引:1,自引:0,他引:1
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Kurisaki K Kurisaki A Valcourt U Terentiev AA Pardali K Ten Dijke P Heldin CH Ericsson J Moustakas A 《Molecular and cellular biology》2003,23(13):4494-4510
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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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