Oncogenic H-Ras G12V and its variants have been shown to inhibit muscle differentiation. However, the role of proto-oncogenic Ras （c-Ras） in muscle differentiation remains unclear. The active GTP-bound form of Ras h...Oncogenic H-Ras G12V and its variants have been shown to inhibit muscle differentiation. However, the role of proto-oncogenic Ras （c-Ras） in muscle differentiation remains unclear. The active GTP-bound form of Ras has been known to associate with diverse effectors including Raf, phosphatidylinositol 3-kinase （PI3K）, RaI-GDS, and other molecules to transmit downstream signals. We hypothesize that c-Ras may stimulate muscle differentiation by selectively activating PI3K, an important mediator for muscle differentiation. In our experiments, inhibition of c-Ras by farnesyltransferase inhibitors and a dominant negative form of H-Ras （Ras S17N） suppressed muscle differentiation. Consistently, individual knockdown of H-Ras, K-Ras, and N-Ras by siRNAs all blocked muscle differentiation. Interestingly, we found that c-Ras preferentially interacts with PI3K rather than its major binding partner c-Raf, during myogenic differentiation, with total c-Ras activity remaining unchanged. PI3K and its downstream myogenic pathway, the Nox2/NF-kB/inducible nitric oxide synthase （iNOS） pathway, were found to be suppressed by inhibition of c-Ras activity during differentiation. Furthermore, expression of a constitutively active form of PI3K completely rescued the differentiation block and reactivated the Nox2/NF-kB/iNOS pathway in c-Ras-inhibited cells. On the ba- sis of our results, we conclude that contrary to oncogenic Ras, proto-oncogenic H-Ras, K-Ras, and N-Ras are directly involved in the promotion of muscle differentiation via PI3K and its downstream signaling pathways. In addition, PI3K pathway activation is associated with a concurrent suppression of the otherwise predominantly activated Raf/ Mek/Erk pathway.展开更多
Nuclear matrix is a delicate proteineous network in eukaryote nucleus, and its functional diversity is becoming increasingly apparent.It is generally acknowledged that nuclear matrix,being a morphological and biochemi...Nuclear matrix is a delicate proteineous network in eukaryote nucleus, and its functional diversity is becoming increasingly apparent.It is generally acknowledged that nuclear matrix,being a morphological and biochemical complex molecular展开更多
目的 :探讨c K ras癌基因与胰腺癌的关系。方法 :查阅近年来的国内外文献 ,对c K ras癌基因与胰腺癌发生的关系进行分析。结果 :胰腺癌中呈现高发的c K ras基因第 12密码字点突变。结论 :检测c K ras基因点突变有助于胰腺癌的早期诊断 ...目的 :探讨c K ras癌基因与胰腺癌的关系。方法 :查阅近年来的国内外文献 ,对c K ras癌基因与胰腺癌发生的关系进行分析。结果 :胰腺癌中呈现高发的c K ras基因第 12密码字点突变。结论 :检测c K ras基因点突变有助于胰腺癌的早期诊断 ,而且是对细胞学。展开更多
c-ras-P21 and Gamma-glutamyltransferase (G-GT) activity and its isoenzymes in rat liver extracts were measured after partial hepatectomy. There were G-GT activity peaks at 12th and 36th hour after operation, while no ...c-ras-P21 and Gamma-glutamyltransferase (G-GT) activity and its isoenzymes in rat liver extracts were measured after partial hepatectomy. There were G-GT activity peaks at 12th and 36th hour after operation, while no distinct isoenzyme patterns were found. P21 protein expression occurred between 48 and 96 hours after partial hepatectomy. These results suggest that the temporary increase of G-GT and P21 protein level is involved in the prereplica-tive stage of liver regeneration.展开更多
文摘Oncogenic H-Ras G12V and its variants have been shown to inhibit muscle differentiation. However, the role of proto-oncogenic Ras （c-Ras） in muscle differentiation remains unclear. The active GTP-bound form of Ras has been known to associate with diverse effectors including Raf, phosphatidylinositol 3-kinase （PI3K）, RaI-GDS, and other molecules to transmit downstream signals. We hypothesize that c-Ras may stimulate muscle differentiation by selectively activating PI3K, an important mediator for muscle differentiation. In our experiments, inhibition of c-Ras by farnesyltransferase inhibitors and a dominant negative form of H-Ras （Ras S17N） suppressed muscle differentiation. Consistently, individual knockdown of H-Ras, K-Ras, and N-Ras by siRNAs all blocked muscle differentiation. Interestingly, we found that c-Ras preferentially interacts with PI3K rather than its major binding partner c-Raf, during myogenic differentiation, with total c-Ras activity remaining unchanged. PI3K and its downstream myogenic pathway, the Nox2/NF-kB/inducible nitric oxide synthase （iNOS） pathway, were found to be suppressed by inhibition of c-Ras activity during differentiation. Furthermore, expression of a constitutively active form of PI3K completely rescued the differentiation block and reactivated the Nox2/NF-kB/iNOS pathway in c-Ras-inhibited cells. On the ba- sis of our results, we conclude that contrary to oncogenic Ras, proto-oncogenic H-Ras, K-Ras, and N-Ras are directly involved in the promotion of muscle differentiation via PI3K and its downstream signaling pathways. In addition, PI3K pathway activation is associated with a concurrent suppression of the otherwise predominantly activated Raf/ Mek/Erk pathway.
文摘Nuclear matrix is a delicate proteineous network in eukaryote nucleus, and its functional diversity is becoming increasingly apparent.It is generally acknowledged that nuclear matrix,being a morphological and biochemical complex molecular
文摘c-ras-P21 and Gamma-glutamyltransferase (G-GT) activity and its isoenzymes in rat liver extracts were measured after partial hepatectomy. There were G-GT activity peaks at 12th and 36th hour after operation, while no distinct isoenzyme patterns were found. P21 protein expression occurred between 48 and 96 hours after partial hepatectomy. These results suggest that the temporary increase of G-GT and P21 protein level is involved in the prereplica-tive stage of liver regeneration.
