Characterization of the inhibition of DNA synthesis in proliferating mink lung epithelial cells by insulin-like growth factor binding protein-3

Wu, Haibin; Kumar, Amit; Tsai, Wen-Chi; Mascarenhas, Desmond; Healey, Judy; Rechler, Matthew M.

doi:10.1002/(sici)1097-4644(20000501)77:2<288::aid-jcb11>3.0.co;2-j

Cited by 25 publications

(41 citation statements)

References 43 publications

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“…Even relatively conservative sequence substitutions in this 14-mer region completely abolished the apoptotic activity of these peptides. We show that the pro-apoptotic actions of MBD peptides are unequivocally IGF-independent, as they are unaffected by the presence of equimolar amounts of [Y60L]-IGF-I, a mutant IGF-I molecule that retains its ability to bind IGFBP-3 but not its cognate receptor IGF-1-R (42).…”

Section: Discussionmentioning

confidence: 95%

Insulin-like Growth Factor-independent Effects Mediated by a C-terminal Metal-binding Domain of Insulin-like Growth Factor Binding Protein-3

Singh

Charkowicz

Mascarenhas

2004

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 95%

Insulin-like Growth Factor-independent Effects Mediated by a C-terminal Metal-binding Domain of Insulin-like Growth Factor Binding Protein-3

Singh

Charkowicz

Mascarenhas

2004

Journal of Biological Chemistry

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“…IGFBP-1 also has IGF-I-independent effects, but it is not expressed by intestinal smooth muscle cells. An IGF-I-independent effect of IGFBP-3 on growth has been identified in a number of mammalian cell types, including mink lung epithelial cells, rat chrondrocytes, and several cell lines derived from breast, lung, prostate, and colon cancers (8,11,26,28,35,40). The ability of endogenous IGFBP-3 to directly regulate intestinal smooth muscle cell growth and the mechanisms involved has not previously been examined.…”

Section: Discussionmentioning

confidence: 99%

IGFBP-3 activates TGF-β receptors and directly inhibits growth in human intestinal smooth muscle cells

Kuemmerle

Murthy

Bowers

2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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We have shown that human intestinal smooth muscle cells produce IGF-I and IGF binding protein-3 (IGFBP-3). Endogenous IGF-I acts in autocrine fashion to stimulate growth of these cells. IGFBP-3 inhibits the binding of IGF-I to its receptor and thereby inhibits IGF-I-stimulated growth. In several carcinoma cell lines and some normal cells, IGFBP-3 regulates growth independently of IGF-I. Two mechanisms for this effect have been identified: IGFBP-3 can directly activate transforming growth factor-β (TGF-β) receptors or it can undergo direct nuclear translocation. The aim of the present study was to determine whether IGFBP-3 acts independently of IGF-I and to characterize the mechanisms mediating this effect in human intestinal smooth muscle cells. The direct effects of IGFBP-3 were determined in the presence of an IGF-I receptor antagonist to eliminate its IGF-I-dependent effects. Affinity labeling of TGF-β receptors (TGF-βRI, TGF-βRII, and TGF-βRV) with 125I-labeled TGF-β1 showed that IGFBP-3 displaced binding to TGF-βRII and TGF-βRV in a concentration-dependent fashion. IGFBP-3 stimulated TGF-βRII-dependent serine phosphorylation (activation) of both TGF-βRI and of its primary substrate, Smad2(Ser465/467). IGFBP-3 also caused IGF-I-independent inhibition of basal [3H]thymidine incorporation. The effects of IGFBP-3 on Smad2 phosphorylation and on smooth muscle cell proliferation were independent of TGF-β1 and were abolished by transfection of Smad2 siRNA. Immunoneutralization of IGFBP-3 increased basal [3H]thymidine incorporation, implying that endogenous IGFBP-3 inhibits proliferation. We conclude that endogenous IGFBP-3 directly inhibits proliferation of human intestinal smooth muscle cells by activation of TGF-βRI and Smad2, an effect that is independent of its effect on IGF-I-stimulated growth.

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“…It is produced by many cell types and appears to inhibit cell growth by IGF-dependent and -independent mechanisms. The putative IGFBP-3 receptor that mediates the IGF-independent growth inhibition was first identified as TbR-V in our laboratory [Leal et al, 1997] and subsequently confirmed by others [Wu et al, 2000]. By analogy with TGF-b [Roberts and Sporn, 1993;Roberts, 1998], the dimeric form (non-covalently linked) of IGFBP-3 interacts with TbR-V in mink lung epithelial cells (Mv1Lu cells) and inhibits growth of these cells [Leal et al, 1997[Leal et al, , 1999.…”

Section: Tbr-v Is Pivotal To Cellular Growth Inhibition By Igfbp-3 Anmentioning

confidence: 92%

“…The identity of TbR-IV has not been confirmed by independent studies [Yamashita et al, 1995]. TbR-V coexpresses with TbR-I, TbR-II, and TbR-III in all normal cell types studied thus far [O'Grady et al, 1991a,b] and also serves as the insulin-like growth factor binding protein-3 (IGFBP-3) receptor, mediating IGF-independent growth inhibition by IGFBP-3 in responsive cells [Leal et al, 1997[Leal et al, , 1999Wu et al, 2000]. TbR-VI and other membrane-associated TGF-b binding proteins are expressed only in specific cell types [Mitchell et al, 1992;Segarini, 1993].…”

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confidence: 99%

TGF‐β control of cell proliferation

Huang

2005

J of Cellular Biochemistry

194

264

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This article focuses on recent findings that the type V TGF-b receptor (TbR-V), which co-expresses with other TGF-b receptors (TbR-I, TbR-II, and TbR-III) in all normal cell types studied, is involved in growth inhibition by IGFBP-3 and TGF-b and that TGF-b activity is regulated by two distinct endocytic pathways (clathrin-and caveolar/lipidraft-mediated). TGF-b is a potent growth inhibitor for most cell types, including epithelial and endothelial cells. The signaling by which TGF-b controls cell proliferation is not well understood. Many lines of evidence indicate that other signaling pathways, in addition to the prominent TbR-I/TbR-II/Smad2/3/4 signaling cascade, are required for mediating TGF-b-induced growth inhibition. Recent studies revealed that TbR-V, which is identical to LRP-1, mediates IGFindependent growth inhibition by IGFBP-3 and mediates TGF-b-induced growth inhibition in concert with TbR-I and TbR-II. In addition, IRS proteins and a Ser/Thr-specific protein phosphatase(s) are involved in the TbR-V-mediated growth inhibitory signaling cascade. The TbR-V signaling cascade appears to cross-talk with the TbR-I/TbR-II, insulin receptor (IR), IGF-I receptor (IGF-IR), integrin and c-Met signaling cascades. Attenuation or loss of the TbR-V signaling cascade may enable carcinoma cells to escape from TGF-b growth control and may contribute to the aggressiveness and invasiveness of these cells via promoting epithelial-to-mesenchymal transdifferentiation (EMT). Finally, the ratio of TGF-b binding to TbR-II and TbR-I is a signal controlling TGF-b partitioning between two distinct endocytosis pathways and resultant TGF-b responsiveness. These recent studies have provided new insights into the molecular mechanisms underlying TGF-binduced cellular growth inhibition, cross-talk between the TbR-V and other signaling cascades, the signal that controls TGF-b responsiveness and the role of TbR-V in tumorigenesis.

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Characterization of the inhibition of DNA synthesis in proliferating mink lung epithelial cells by insulin-like growth factor binding protein-3

Cited by 25 publications

References 43 publications

Insulin-like Growth Factor-independent Effects Mediated by a C-terminal Metal-binding Domain of Insulin-like Growth Factor Binding Protein-3

Insulin-like Growth Factor-independent Effects Mediated by a C-terminal Metal-binding Domain of Insulin-like Growth Factor Binding Protein-3

IGFBP-3 activates TGF-β receptors and directly inhibits growth in human intestinal smooth muscle cells

TGF‐β control of cell proliferation

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