Cellular growth inhibition by IGFBP‐3 and TGF‐β1 requires LRP‐1

  title={Cellular growth inhibition by IGFBP‐3 and TGF‐$\beta$1 requires LRP‐1},
  author={Shuan Shian Huang and Thai-Yen Ling and Wen-Fang Tseng and Yen-Hwa Huang and Fen-Mei Tang and Sandra M Leal and Jung San Huang},
  journal={The FASEB Journal},
  pages={2068 - 2081}
The type V TGF‐β receptor (TβR‐V)/IGFBP‐3 receptor mediates the IGF‐independent growth inhibition induced by IGFBP‐3. It also mediates the growth inhibitory response to TGF‐β1 in concert with other TGF‐β receptor types, and its loss may contribute to the malignant phenotype of human carcinoma cells. Here we demonstrate that TβR‐V is identical to LRP‐1/α2M receptor as shown by MALDI‐TOF analysis of tryptic peptides of TβR‐V purified from bovine liver. In addition, 125I‐IGFBP‐3 affinity‐labeled T… 
Identification of insulin receptor substrate proteins as key molecules for the TβR‐V/LRP‐1‐mediated growth inhibitory signaling cascade in epithelial and myeloid cells
It is found that insulin and IGF‐I antagonize growth inhibition by IGFBP‐3 in mink lung epithelial cells (Mv1Lu cells) stimulated by serum and this results suggest that IRS‐1 and IRS‐2 are key molecules for the TβR‐V/LRP‐1‐mediated growth inhibitory signaling cascade.
IGFBP‐3 and TGF‐β inhibit growth in epithelial cells by stimulating type V TGF‐β receptor (TβR‐V)‐mediated tumor suppressor signaling
Small molecule TGF‐β enhancers, which potentiate T GF‐β growth inhibition by enhancing TβR‐I–T βR‐II‐mediated canonical signaling and thus activating Tβr‐V‐mediated tumor suppressor signaling cascade (TβR•V/IRS‐2/PP1/pRb), could be used to prevent and treat carcinoma.
TGF‐β control of cell proliferation
These recent studies have provided new insights into the molecular mechanisms underlying TGF‐β‐induced cellular growth inhibition, cross‐talk between the TβR‐V and other signaling cascades, the signal that controls T GF‐β responsiveness and the role of Tβr‐V in tumorigenesis.
Cholesterol modulates cellular TGF‐β responsiveness by altering TGF‐β binding to TGF‐β receptors
The results indicate that high plasma cholesterol levels may contribute to the pathogenesis of certain diseases (e.g., atherosclerosis) by suppressing TGF‐β responsiveness.
Dual effects of IGFBP‐3 on endothelial cell apoptosis and survival: Involvement of the sphingolipid signaling pathways
  • R. Granata, L. Trovato, E. Ghigo
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2004
It is reported that IGFBP‐3 exerts dual effects on HUVEC, potentiating doxorubicin‐induced apoptosis but enhancing survival in serum‐starved conditions, providing evidence that IGF BP‐3 differentially regulates endothelial cell apoptosis by involvement of the sphingolipid signaling pathways.
Ethanol Enhances TGF‐β Activity by Recruiting TGF‐β Receptors From Intracellular Vesicles/Lipid Rafts/Caveolae to Non‐Lipid Raft Microdomains
It is demonstrated that ethanol enhances TGF‐β‐stimulated Luciferase activity with a maximum of 0.5–1% (v/v) in Mv1Lu cells stably expressing a luciferase reporter gene containing Smad2‐dependent elements, and suggested thatanol enhances canonical TGF­β signaling by increasing non‐lipid raft microdomain localization of the TGF•β receptors.
TGF‐β signaling: A tale of two responses
TGF‐β signaling in epithelial cells and fibroblasts is reviewed with a focus on understanding the mechanisms of TGF‐ β versatility, which is implicated in promoting carcinogenesis and fibrotic diseases.
A Novel Modulatory Mechanism of Transforming Growth Factor-β Signaling through Decorin and LRP-1*
This work unveils a new regulatory mechanism for TGF-β signaling by decorin and LRP-1 and involves phosphatidylinositol 3-kinase activity.


Characterization of the inhibition of DNA synthesis in proliferating mink lung epithelial cells by insulin‐like growth factor binding protein‐3
The ability of Leu60‐IGF‐I to decrease both the inhibition of DNA synthesis by IGF BP‐3 and IGFBP‐3 binding to the ∼︁400‐kDa receptor is consistent with the hypothesis that the∽kDa IGFBP-3 receptor mediates the inhibitionof CCL64 DNA synthesis.
The Type V Transforming Growth Factor β Receptor Is the Putative Insulin-like Growth Factor-binding Protein 3 Receptor*
It is shown that recombinant human IGFBP-3 inhibits125I-transforming growth factor (TGF)-β1 binding to the type V TGF-β receptor in mink lung epithelial cells and indicates that IGF BP-3 is a functional ligand for thetype V T GF- β receptor.
Function of the Type V Transforming Growth Factor β Receptor in Transforming Growth Factor β-induced Growth Inhibition of Mink Lung Epithelial Cells*
TGF-β stimulation resulted in the growth inhibition of wild-type mink lung epithelial cells and to a lesser extent of the type I and type II T GF-β receptor-defective mutants, although higher concentrations of TGF- β were required for thegrowth inhibition of these mutants.
A Novel Mechanism for Regulating Transforming Growth Factor β (TGF-β) Signaling
It is established, for the first time, a protein that interacts with the cytoplasmic domain of the type III receptor is regulated at the protein level and that increased expression of the types I, II, and type III receptors is sufficient to enhance TGF-β signaling.
Transforming Growth Factor β Peptide Antagonists and Their Conversion to Partial Agonists*
The results suggest that the (W/R)XXD motif is important for the activities of these TGF-β peptide antagonists and that this motif may be the active site sequence of T GF-β.
Reduced Expression of Transforming Growth Factor β Type I Receptor Contributes to the Malignancy of Human Colon Carcinoma Cells*
Results indicate that low RI expression can be a limiting factor for response to exogenous TGFβ, as well as TGF β autocrine-negative activity, and that reduction of RIexpression can contribute to malignant progression.
Internalization-Dependent and -Independent Requirements for Transforming Growth Factor β Receptor Signaling via the Smad Pathway
Evidence is provided that, whereas type I receptor phosphorylation and association of SARA and Smad2 with the TGF-βR complex take place independently of clathrin lattice formation, Smad 2 or Smad3 activation and downstream signaling only occur after endocytic vesicle formation, TGF -βR endocytosis is required to propagate signaling via the Smad pathway.
Betaglycan inhibits TGF-beta signaling by preventing type I-type II receptor complex formation. Glycosaminoglycan modifications alter betaglycan function.
The data indicate that betaglycan can function as a potent inhibitor of TGF-beta signaling by a novel mechanism and provide support for an essential but complex role for proteoglycan co-receptors in growth factor signaling.
TGF-β inhibits p70 S6 kinase via protein phosphatase 2A to induce G1 arrest
Evidence is presented for a second, parallel, TGF-β-dependent pathway for cell cycle arrest, achieved via inhibition of p70s6k, which modulates the translational and posttranscriptional control of cell cycle progression.