共查询到20条相似文献,搜索用时 31 毫秒
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Leong ML Maiyar AC Kim B O'Keeffe BA Firestone GL 《The Journal of biological chemistry》2003,278(8):5871-5882
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Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor 总被引:154,自引:0,他引:154
Brunet A Bonni A Zigmond MJ Lin MZ Juo P Hu LS Anderson MJ Arden KC Blenis J Greenberg ME 《Cell》1999,96(6):857-868
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Microtubule binding to Smads may regulate TGF beta activity 总被引:16,自引:0,他引:16
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Bailey JP Nieport KM Herbst MP Srivastava S Serra RA Horseman ND 《Molecular endocrinology (Baltimore, Md.)》2004,18(5):1171-1184
Both prolactin (PRL) and TGF-beta regulate cell survival in mammary epithelial cells, but their mechanisms of interactions are not known. In primary mammary epithelial cells and the HC11 mouse mammary epithelial cell line, PRL prevented TGF-beta-induced apoptosis, as measured by terminal deoxynucleotidyltransferase dUTP nick-end labeling staining and caspase-3 activation. This effect depended on phosphatidyl inositol triphosphate kinase (PI3K). PI3K activates a downstream serine/threonine kinase, Akt; therefore, we investigated the role of Akt in the interaction between PRL and TGF-beta signaling. Akt activity was inhibited by TGF-beta over a 20- to 60-min time course. In TGF-beta-treated cells, PRL disinhibited Akt in a PI3K-dependent manner. Expression of dominant negative Akt blocked the protective effect of PRL in TGF-beta-induced apoptosis. Transgenic mice overexpressing a dominant-negative TGF-beta type II receptor (DNIIR) in the mammary epithelium undergo hyperplastic alveolar development, and this effect was PRL dependent. Involution in response to teat sealing was slowed by overexpression of DNIIR; furthermore, Akt and forkhead phosphorylation increased in the sealed mammary glands of DNIIR mice. Thus, Akt appears to be an essential component of the interaction between PRL and TGF-beta signaling in mammary epithelial cells both in vitro and in vivo. 相似文献
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A member of Forkhead transcription factor FKHRL1 is a downstream effector of STI571-induced cell cycle arrest in BCR-ABL-expressing cells 总被引:6,自引:0,他引:6
Komatsu N Watanabe T Uchida M Mori M Kirito K Kikuchi S Liu Q Tauchi T Miyazawa K Endo H Nagai T Ozawa K 《The Journal of biological chemistry》2003,278(8):6411-6419
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TGF beta-induced focal complex formation in epithelial cells is mediated by activated ERK and JNK MAP kinases and is independent of Smad4 总被引:5,自引:0,他引:5
Imamichi Y Waidmann O Hein R Eleftheriou P Giehl K Menke A 《Biological chemistry》2005,386(3):225-236
Advanced malignancies often exhibit increased concentrations of transforming growth factor-beta (TGF beta), which has been suggested to promote invasion and metastasis. While inhibition of epithelial cell proliferation in response to TGF beta is mainly mediated by the well-characterised Smad pathway, the molecular mechanism leading to TGF beta-induced invasiveness and metastasis are largely unknown. To elucidate these mechanisms, we compared TGF beta1 signalling in MCF-7 and the Smad4-negative MDA-MB-468 breast cancer cells. Both cell lines react to TGF beta1 treatment with decreased subcortical actin and increased numbers of focal contacts. TGF beta1-induced cell migration was strongly dependent on the activation of extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK). These mitogen-activated protein kinases were phosphorylated in response to TGF beta and subsequently translocated into focal contacts. Inhibition of the TGF beta type I receptor ALK5 slightly reduced phosphorylation of ERK in MCF-7 cells, but neither inhibited phosphorylation of ERK in MDA-MB-468 cells nor TGF beta1-induced migration of both cell lines. In contrast, ALK5 inhibition effectively blocked Smad2 phosphorylation. In addition to ERK and JNK, the monomeric GTPase RhoA was activated by TGF beta1 and necessary for TGF beta-induced migration. Taken together, our study identifies a role of ERK and JNK activation and association of activated MAPKs with focal complexes in TGF beta1-induced cell migration in epithelial cells. These TGF beta-dependent processes were mediated independently of Smad4. 相似文献