Báo cáo khóa học: Nerve growth factor mediates activation of the Smad pathway in PC12 cells doc

... represents the limiting component of TGF-b1 signaling in PC12 cells. Smad2 phosphorylationwasanalysedinparentalPC12cellsandinstablePC1 2cells expressing TbRII-wt under the control of a doxycycline-inducible ... leads to activation of the Smad pathway independent of TGF-b. In contrast to TGF-b signaling, activation of Smad3 by nerve growth factor does not occur via phospho-rylation of the C-terminal SSXS-motif, ... stimulation of PC12 cells results in activation of the Smad pathway independently of TGF-b1. This activation is direct andresults in nuclear translocation of Smad3 within only30 min of NGF treatment....

Tài liệu Báo cáo khoa học: Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer ppt

... because it stimulated the proliferation of epithelial cells [1]. In 1972, the aminoacid sequence of the EGF was determined. The pres-ence of a speciﬁc binding site for EGF, the EGF recep-tor ... Uponbinding its ligands, dynamic conformational changes occur in both extra-cellular and intracellular domains of the receptor tyrosine kinases, resulting in the transphosphorylation of tyrosine ... extracellulardomain is subdivided further into four domains. The tyrosine kinase domain consists of an N-lobe and aC-lobe, and ATP binds to the cleft formed betweenthese two lobes. The C-terminal regulatory...

Tài liệu Báo cáo khoa học: Epidermal growth factor receptor in relation to tumor development: EGFR-targeted anticancer therapy doc

... binding to the tyrosine kinase pocket of the receptor, therebyinhibiting receptor tyrosine kinase activity and EGFRsignaling pathways (Fig. 1). Early clinical studiesshowed that a subset of ... markersthat have the potential to improve the clinical effectiveness of EGFR-targeted therapies. This minireview summarizes the emerging role of molec-ular proﬁling in guiding the clinical use of anti-EGFR ... results in EGFR signaling pathways beingturned off and the cancer cells undergoing apoptosis.Moreover, EGFR mutations result in repositioning of critical residues surrounding the ATP-binding cleft...

Báo cáo khoa học: Epidermal growth factor receptor-regulated miR-125a-5p – a metastatic inhibitor of lung cancer potx

... expression in a subset of human lung cancersTo gain further insights into the role of miR-125a-5p in lung carcinogenesis and to examine the clinical rele-vance of our ﬁndings, we investigated the ... further determine the requirement forEGFR signaling in the expression of miRNA listed in Table 1, we blocked EGFR signaling with geﬁtinib.Geﬁtinib is an inhibitor of tyrosine kinase that competeswith ... competeswith ATP for binding to the intracellular kinase domain,preventing receptor activation and the engagement of downstream signaling transducers [12]. Thus, it has beenwidely used to interfere with...

Báo cáo khoa học: Hepatocyte growth factor activator (HGFA): a serine protease that links tissue injury to activation of hepatocyte growth factor pdf

... examples of latent growth factors have already been reported. Insulin-like growth factors are inactive when bound to insulin-like growth factor- binding proteins. Transforming growth factor- b ... that single-chain HGFwas inactive in the presence of serine protease inhibi-tors in a hepatocyte proliferation assay, whereas the two-chain form was active even in the presence of the inhibitors ... [11]. The antibody reactswith both the single-chain and two-chain forms of HGF, giving positive bands at 92 and 62 kDa, respec-tively. By scanning of the 92 and 62 kDa bands, the ratio of the single-chain...

Báo cáo khoa học: Hepatocyte growth factor activator (HGFA): molecular structure and interactions with HGFA inhibitor-1 (HAI-1) doc

... multidomain inhibitor containing two Kunitzdomains, of which only the N-terminal Kunitz domain-1 (KD1) inhibitsenzymatic activity. In the structure of the KD1–HGFA complex, the inhibitor interacts ... predict, as in the case of the related aprotinin–prostasin complex, in which the 99-loop moves away from the substrate-bindingcleft to accommodate the Kunitz-type inhibitor aproti-nin [15]. In some ... rapidly resynthesized, so that the intact form of the Kunitz domain inhibitor predominates in the crystal structure [35]. According to this model, the intact KD1 peptide bond in the KD1–HGFA...

Báo cáo khoa học: Hepatocyte growth factor activator (HGFA): its regulation by protein C inhibitor ppt

... thatthrombin interacts with PCI, depending on the length of PCI’s reactive center loop to align the heparin-bind-ing sites of the two proteins, suggesting that the cofac-tor activity of heparin depends ... the concentration of HGFA–PCI increased in a time-dependent manner.PCI also inhibits the HGFA-catalyzed activation of HGF precursor [26]. In the absence of PCI, almost all of the single-chain ... byHGFA, releasing the 98 kDa disulﬁde-linked activeform of HGF. In contrast, in the presence of PCI-pre-treated HGFA, the single-chain HGF precursor wasminimally converted into the two-chain form.HGFA–PCI...

Báo cáo khoa học: Hepatocyte growth factor activator (HGFA): pathophysiological functionsin vivo potx

... understanding of the roles of HGFA in physiological and pathological settings.Synthesis and distribution of HGFA in vivoHGFA is secreted mainly by the liver, and circulates in the plasma as a single-chain ... signaling.Since the discovery of HGFA, only a limited num-ber of in vivo studies have been published describing the role of HGFA in physiological processes (Table 1). The roles of HGFA during the ... of HGFA in the acti-vation of pro-HGF ⁄ SF in injured tissues was initiallyconﬁrmed in a rat model of liver injury induced bycarbon tetrachloride [24,31]. In that study, the genera-tion of...

Báo cáo khoa học: Hepatocyte growth factor activator is a serum activator of single-chain precursor macrophage-stimulating protein potx

... mechanical wound in the dorsalskin of mice and examined the in ltration of macro-phages by measuring the CD68 mRNA level. One dayafter injury, the levels of CD68 mRNA in the wounds of HGFA)/)mice ... proteinase(s)MacrophagesEpithelial cells Tumour cells Endothelial cells Factor XIa Factor XIIaFig. 7. Hypothetical model for the activation of pro-MSP. There may be diverse pathways for the activation ... Wound ﬂuids in the injured tissues contain other pro-MSP acti-vators, such as epidermal growth factor- binding protein (EGF-BP) and nerve growth factor c (NGF-c) [10]. The effects of EGF-BP and...

Tài liệu Báo cáo khoa học: Helix mobility and recognition function of the rat thyroid transcription factor 1 homeodomain – hints from 15N-NMR relaxation studies pdf

... well-knownclass of DNA-binding domains occurring in a largefamily of transcription activators involved in the determination of cell development [1–3]. The tertiarystructure of the HD of rat thyroid ... suggesting the occurrence of eithera kinking or tightening of the local geometry. Asimilar discontinuity had been noted in solution also in the Antp HD [8,9] and the Antp (C39S) HD [10],and indeed, ... related to the dis-tribution of the energy between the overall tumblingand the internal mobility, and is indicative of the degree of internal restraint of each15N–1H vectormotion. In Fig....

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