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Title: ISOFORM-SPECIFIC ACTIVATION OF LATENT TRANSFORMING GROWTHFACTOR-beta (LTGF-beta) BY REACTIVE OXYGEN SPECIES

Abstract

No abstract prepared.

Authors:
; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
Sponsoring Org.:
USDOE Director. Office of Science. Biological andEnvironmental Research
OSTI Identifier:
923339
Report Number(s):
LBNL-60367
Journal ID: ISSN 0033-7587; RAREAE; R&D Project: 442301; BnR: KP1102020; TRN: US200804%%995
DOE Contract Number:
DE-AC02-05CH11231
Resource Type:
Journal Article
Resource Relation:
Journal Name: RADIATION RESEARCH; Journal Volume: 166; Related Information: Journal Publication Date: 2006
Country of Publication:
United States
Language:
English
Subject:
59; OXYGEN COMPOUNDS; GROWTH FACTORS; CHEMICAL ACTIVATION

Citation Formats

Jobling, Michael F., Mott, Joni D., Finnegan, Monica T., Jurukovski, Vladimir, Erickson, Anna C., Walian, Peter J., Taylor, ScottE., Ledbetter, Steven, Lawrence, Catherine M., Rifkin, Daniel B., and Barcellos-Hoff, Mary Helen. ISOFORM-SPECIFIC ACTIVATION OF LATENT TRANSFORMING GROWTHFACTOR-beta (LTGF-beta) BY REACTIVE OXYGEN SPECIES. United States: N. p., 2006. Web. doi:10.1667/RR0695.1.
Jobling, Michael F., Mott, Joni D., Finnegan, Monica T., Jurukovski, Vladimir, Erickson, Anna C., Walian, Peter J., Taylor, ScottE., Ledbetter, Steven, Lawrence, Catherine M., Rifkin, Daniel B., & Barcellos-Hoff, Mary Helen. ISOFORM-SPECIFIC ACTIVATION OF LATENT TRANSFORMING GROWTHFACTOR-beta (LTGF-beta) BY REACTIVE OXYGEN SPECIES. United States. doi:10.1667/RR0695.1.
Jobling, Michael F., Mott, Joni D., Finnegan, Monica T., Jurukovski, Vladimir, Erickson, Anna C., Walian, Peter J., Taylor, ScottE., Ledbetter, Steven, Lawrence, Catherine M., Rifkin, Daniel B., and Barcellos-Hoff, Mary Helen. Wed . "ISOFORM-SPECIFIC ACTIVATION OF LATENT TRANSFORMING GROWTHFACTOR-beta (LTGF-beta) BY REACTIVE OXYGEN SPECIES". United States. doi:10.1667/RR0695.1.
@article{osti_923339,
title = {ISOFORM-SPECIFIC ACTIVATION OF LATENT TRANSFORMING GROWTHFACTOR-beta (LTGF-beta) BY REACTIVE OXYGEN SPECIES},
author = {Jobling, Michael F. and Mott, Joni D. and Finnegan, Monica T. and Jurukovski, Vladimir and Erickson, Anna C. and Walian, Peter J. and Taylor, ScottE. and Ledbetter, Steven and Lawrence, Catherine M. and Rifkin, Daniel B. and Barcellos-Hoff, Mary Helen},
abstractNote = {No abstract prepared.},
doi = {10.1667/RR0695.1},
journal = {RADIATION RESEARCH},
number = ,
volume = 166,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2006},
month = {Wed Feb 01 00:00:00 EST 2006}
}
  • No abstract prepared.
  • Transforming growth factor (TGF)-{beta}1, -{beta}2, and -{beta}3 are 25-kDa homodimeric polypeptides that play crucial nonoverlapping roles in embryogenesis, tissue development, carcinogenesis, and immune regulation. Here we report the 3.0-{angstrom} resolution crystal structure of the ternary complex between human TGF-{beta}1 and the extracellular domains of its type I and type II receptors, T{beta}RI and T{beta}RII. The TGF-{beta}1 ternary complex structure is similar to previously reported TGF-{beta}3 complex except with a 10{sup o} rotation in T{beta}RI docking orientation. Quantitative binding studies showed distinct kinetics between the receptors and the isoforms of TGF-{beta}. T{beta}RI showed significant binding to TGF-{beta}2 and TGF-{beta}3 but notmore » TGF-{beta}1, and the binding to all three isoforms of TGF-{beta} was enhanced considerably in the presence of T{beta}RII. The preference of TGF-{beta}2 to T{beta}RI suggests a variation in its receptor recruitment in vivo. Although TGF-{beta}1 and TGF-{beta}3 bind and assemble their ternary complexes in a similar manner, their structural differences together with differences in the affinities and kinetics of their receptor binding may underlie their unique biological activities. Structural comparisons revealed that the receptor-ligand pairing in the TGF-{beta} superfamily is dictated by unique insertions, deletions, and disulfide bonds rather than amino acid conservation at the interface. The binding mode of T{beta}RII on TGF-{beta} is unique to TGF-{beta}s, whereas that of type II receptor for bone morphogenetic protein on bone morphogenetic protein appears common to all other cytokines in the superfamily. Further, extensive hydrogen bonds and salt bridges are present at the high affinity cytokine-receptor interfaces, whereas hydrophobic interactions dominate the low affinity receptor-ligand interfaces.« less
  • No abstract prepared.
  • Nuclear-Factor-{kappa}B (NF-{kappa}{beta} can counteract transforming growth factor-{beta}1 (TGF-{beta}1)-induced apoptosis in malignant hepatocytes through up-regulation of its downstream genes, such as X-linked inhibitor of apoptosis protein (XIAP). Reports have demonstrated that TGF-{beta}1 can induce oxidative stress, and c-Jun N-terminal Kinase1 (JNK1) is indispensable for TGF-{beta}1-induced apoptosis pathway, but the relationship between radical oxygen species (ROS) and the activation of JNKs is still unclear. In the present study, we found that ROS can induce JNK activation in TGF-{beta}1 mediated apoptosis in hepatocytes. The inhibitors of hydrogen peroxide and superoxide, which were produced by mitochondria under stress, could inhibit the phosphorylation of c-Junmore » in XIAP knockdown cells. In conclusion, it is the first time to show that both NF-{kappa}B and antioxidants can counteract TGF-{beta}1-induced apoptosis in hepatic cell death through JNK1 pathway.« less
  • Fibronectin (FN) isoform expression is altered during chondrocyte commitment and maturation, with cartilage favoring expression of FN isoforms that includes the type II repeat extra domain B (EDB) but excludes extra domain A (EDA). We and others have hypothesized that the regulated splicing of FN mRNAs is necessary for the progression of chondrogenesis. To test this, we treated the pre-chondrogenic cell line ATDC5 with transforming growth factor-{beta}1, which has been shown to modulate expression of the EDA and EDB exons, as well as the late markers of chondrocyte maturation; it also slightly accelerates the early acquisition of a sulfated proteoglycanmore » matrix without affecting cell proliferation. When chondrocytes are treated with TGF-{beta}1, the EDA exon is preferentially excluded at all times whereas the EDB exon is relatively depleted at early times. This regulated alternative splicing of FN correlates with the regulation of alternative splicing of SRp40, a splicing factor facilitating inclusion of the EDA exon. To determine if overexpression of the SRp40 isoforms altered FN and FN EDA organization, cDNAs encoding these isoforms were overexpressed in ATDC5 cells. Overexpression of the long-form of SRp40 yielded an FN organization similar to TGF-{beta}1 treatment; whereas overexpression of the short form of SRp40 (which facilitates EDA inclusion) increased formation of long-thick FN fibrils. Therefore, we conclude that the effects of TGF-{beta}1 on FN splicing during chondrogenesis may be largely dependent on its effect on SRp40 isoform expression.« less