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排序方式: 共有2935条查询结果,搜索用时 15 毫秒
931.
Takahiro Sawada Daiki Arai Xuefeng Jing Kenryo Furushima Qingfa Chen Kazuki Kawakami Hideyuki Yokote Masayasu Miyajima Kazushige Sakaguchi 《PloS one》2015,10(5)
Ephs and FGFRs belong to a superfamily of receptor tyrosine kinases, playing important roles in stem cell biology. We previously reported that EphA4 and FGFR form a heterodimer following stimulation with ligands, trans-activating each other and signaling through a docking protein, FRS2α, that binds to both receptors. Here, we investigated whether the interaction between EphA4 and FGFRs can be generalized to other Ephs and FGFRs, and, in addition, examined the downstream signal mediating their function in embryonic neural stem/progenitor cells. We revealed that various Ephs and FGFRs interact with each other through similar molecular domains. When neural stem/progenitor cells were stimulated with FGF2 and ephrin-A1, the signal transduced from the EphA4/FGFR/FRS2α complex enhanced self-renewal, while stimulation with ephrin-A1 alone induced neuronal differentiation. The downstream signal required for neuronal differentiation appears to be MAP kinase mainly linked to the Ras family of G proteins. MAP kinase activation was delayed and sustained, distinct from the transient activation induced by FGF2. Interestingly, this effect on neuronal differentiation required the presence of FGFRs. Specific FGFR inhibitor almost completely abolished the function of ephrin-A1 stimulation. These findings suggest that the ternary complex of EphA, FGFR and FRS2α formed by ligand stimulation regulates self-renewal and differentiation of mouse embryonic neural stem/progenitor cells by ligand-specific fine tuning of the downstream signal via FRS2α. 相似文献
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A phosphorylated protein with a molecular mass of 25,000 (pp25) is involved in Xenopus laevis vitellogenin B1 and partially overlaps with phosvitin and lipovitellin 2. The protease responsible for pp25 degradation was studied in vitro since this occurs during embryogenesis. Initially, a protease thought to be a contaminant of the purified pp25 preparation was analyzed and an antipain-sensitive protease presumed to be involved. When commercially available proteases were examined, pp25 was not degraded by calpain I or 20S proteasome, but it was degraded by cathepsin L in vitro. A survey of the protease responsible for pp25 degradation in the cytoplasm of Xenopus oocytes found partially purified pp25 was degraded in partly antipain-sensitive manner. These results suggest that an antipain-sensitive protease or cathepsin L (or a related protease) is a candidate for pp25 degradation. 相似文献
936.
Toshiaki Fujihashi Takahiro Ogata Tetsuo Ohkuma Tohru Endo Akira Kaji 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):295-310
Abstract A new cyclic AMP analogue, adenosine- 3′, 5′-cyclic methyl phosphonate (cAMP-Me) was chemically synthesized. This compound was not a substrate for phosphodiesterase, and it did not activate cAMP-dependent protein kinases (type I or type II). However, it inhibited cAMP phosphodiesterase and protein kinase at milimolar concentration levels. It also inhibited malignant cell proliferation in vitro. 相似文献
937.
Itoh Kazuhiro Iwasaki Hiromichi Negoro Eiju Shigemi Hiroko Tokimatsu Issei Tsutani Hiroshi Yamauchi Takahiro 《Mycopathologia》2021,186(1):113-117
Mycopathologia - Invasive trichosporonosis is a rare and lethal fungal infection that occurs in immunocompromised patients. Breakthrough trichosporonosis can occur in patients treated with... 相似文献
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Okita K Matsumura Y Sato Y Okada A Morizane A Okamoto S Hong H Nakagawa M Tanabe K Tezuka K Shibata T Kunisada T Takahashi M Takahashi J Saji H Yamanaka S 《Nature methods》2011,8(5):409-412
We report a simple method, using p53 suppression and nontransforming L-Myc, to generate human induced pluripotent stem cells (iPSCs) with episomal plasmid vectors. We generated human iPSCs from multiple donors, including two putative human leukocyte antigen (HLA)-homozygous donors who match ~20% of the Japanese population at major HLA loci; most iPSCs are integrated transgene-free. This method may provide iPSCs suitable for autologous and allologous stem-cell therapy in the future. 相似文献
940.
Saiki S Sasazawa Y Imamichi Y Kawajiri S Fujimaki T Tanida I Kobayashi H Sato F Sato S Ishikawa K Imoto M Hattori N 《Autophagy》2011,7(2):176-187
Caffeine is one of the most frequently ingested neuroactive compounds. All known mechanisms of apoptosis induced by caffeine act through cell cycle modulation or p53 induction. It is currently unknown whether caffeine-induced apoptosis is associated with other cell death mechanisms, such as autophagy. Herein we show that caffeine increases both the levels of microtubule-associated protein 1 light chain 3-II and the number of autophagosomes, through the use of western blotting, electron microscopy and immunocytochemistry techniques. Phosphorylated p70 ribosomal protein S6 kinase (Thr389), S6 ribosomal protein (Ser235/236), 4E-BP1 (Thr37/46) and Akt (Ser473) were significantly decreased by caffeine. In contrast, ERK1/2 (Thr202/204) was increased by caffeine, suggesting an inhibition of the Akt/mTOR/p70S6K pathway and activation of the ERK1/2 pathway. Although insulin treatment phosphorylated Akt (Ser473) and led to autophagy suppression, the effect of insulin treatment was completely abolished by caffeine addition. Caffeine-induced autophagy was not completely blocked by inhibition of ERK1/2 by U0126. Caffeine induced reduction of mitochondrial membrane potentials and apoptosis in a dose-dependent manner, which was further attenuated by the inhibition of autophagy with 3-methyladenine or Atg7 siRNA knockdown. Furthermore, there was a reduced number of early apoptotic cells (annexin V positive, propidium iodide negative) among autophagy-deficient mouse embryonic fibroblasts treated with caffeine than their wild-type counterparts. These results support previous studies on the use of caffeine in the treatment of human tumors and indicate a potential new target in the regulation of apoptosis. 相似文献