共查询到20条相似文献,搜索用时 31 毫秒
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Nuclear translocation of Smad proteins is a critical step in signal transduction of transforming growth factor beta (TGF-beta) and bone morphogenetic proteins (BMPs). Using nuclear accumulation of the Drosophila Smad Mothers against Decapentaplegic (Mad) as the readout, we carried out a whole-genome RNAi screening in Drosophila cells. The screen identified moleskin (msk) as important for the nuclear import of phosphorylated Mad. Genetic evidence in the developing eye imaginal discs also demonstrates the critical functions of msk in regulating phospho-Mad. Moreover, knockdown of importin 7 and 8 (Imp7 and 8), the mammalian orthologues of Msk, markedly impaired nuclear accumulation of Smad1 in response to BMP2 and of Smad2/3 in response to TGF-beta. Biochemical studies further suggest that Smads are novel nuclear import substrates of Imp7 and 8. We have thus identified new evolutionarily conserved proteins that are important in the signal transduction of TGF-beta and BMP into the nucleus. 相似文献
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Regulation of cell proliferation by Smad proteins 总被引:40,自引:0,他引:40
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New insights into TGF-beta-Smad signalling 总被引:1,自引:0,他引:1
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Constitutive phosphorylation and nuclear localization of Smad3 are correlated with increased collagen gene transcription in activated hepatic stellate cells 总被引:36,自引:0,他引:36
Inagaki Y Mamura M Kanamaru Y Greenwel P Nemoto T Takehara K Ten Dijke P Nakao A 《Journal of cellular physiology》2001,187(1):117-123
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TGF-beta signaling from receptors to the nucleus 总被引:13,自引:0,他引:13
Roberts AB 《Microbes and infection / Institut Pasteur》1999,1(15):1265-1273
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Signaling inputs converge on nuclear effectors in TGF-beta signaling 总被引:17,自引:0,他引:17
Recent studies have consolidated the pivotal role of Smads as intracellular effectors of TGF-beta family members. Upon binding to their specific type I and type II serine/threonine kinase receptors, each family member activates a particular subset of Smad proteins. Activated, receptor-regulated Smads form hetero-oligomeric complexes with common-partner Smads that translocate into the nucleus, where they control the expression of target genes in a cell-type-specific manner. Smads appear to function not only as nuclear effectors for TGF-beta family members, but as signal integrators within an extensive intracellular network. 相似文献
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Functional characterization of transforming growth factor beta signaling in Smad2- and Smad3-deficient fibroblasts 总被引:12,自引:0,他引:12
Piek E Ju WJ Heyer J Escalante-Alcalde D Stewart CL Weinstein M Deng C Kucherlapati R Bottinger EP Roberts AB 《The Journal of biological chemistry》2001,276(23):19945-19953
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TGF-beta and the Smad signal transduction pathway. 总被引:31,自引:0,他引:31
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The Drosophila transforming growth factor beta (TGF-beta) homolog Decapentaplegic (Dpp) acts as a morphogen that forms a long-range concentration gradient to direct the anteroposterior patterning of the wing. Both planar transcytosis initiated by Dynamin-mediated endocytosis and extracellular diffusion have been proposed for Dpp movement across cells. In this work, we found that Dpp is mainly extracellular, and its extracellular gradient coincides with its activity gradient. We demonstrate that a blockage of endocytosis by the dynamin mutant shibire does not block Dpp movement but rather inhibits Dpp signal transduction, suggesting that endocytosis is not essential for Dpp movement but is involved in Dpp signaling. Furthermore, we show that Dpp fails to move across cells mutant for dally and dally-like (dly), two Drosophila glypican members of heparin sulfate proteoglycan (HSPG). Our results support a model in which Dpp moves along the cell surface by restricted extracellular diffusion involving the glypicans Dally and Dly. 相似文献
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Preferential utilization of Imp7/8 in nuclear import of Smads 总被引:1,自引:0,他引:1
Trafficking of Smad proteins between the cytoplasm and nucleus is a critical component of transforming growth factor beta (TGF-beta) signal transduction. Smad4 translocates into the nucleus either in response to TGF-beta stimulation or when its nuclear export is blocked by leptomycin B (LMB). We demonstrate that both TGF-beta-induced and basal state spontaneous nuclear import of Smad4 require importin 7 and 8 (Imp7,8). Our data suggest that in the nuclear import of Smad4, the role of Imp8 is irreplaceable by Imp7, and that Smads preferentially bind Imp8. Interestingly, in contrast to its mammalian counterpart Smad4, Drosophila Medea appears to utilize different mechanisms for TGF-beta-induced or basal state nuclear accumulation, with the latter independent of Msk (Drosophila Imp7/8) function. In addition, overexpression of Imp8 alone was sufficient to cause an increased concentration of Smad1, 3 and 4 in the nucleus, but had very limited effects on Smad2. These observations suggest selective involvement of Imp8/Msk in nuclear import of different Smads under different conditions. 相似文献
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