Insulin-like growth factor binding protein (IGFBP) signalling

Ricort, Jean‐Marc

doi:10.1016/j.ghir.2004.02.002

Cited by 49 publications

(38 citation statements)

References 64 publications

(95 reference statements)

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“…They include induction and activation of Stat1 (38), phosphorylation of Smad2 and -3 (55,81), and stimulation of phosphotyrosine phosphatase or phosphatidylinositol 3-kinase and increasing intracellular Ca 2ϩ (reviewed in Ref. 43). Antisense oligonucleotide to Stat1 blocked IGFBP-3-induced apoptosis in a rat chon- A, Pre-YFP-IGFBP-3 is synthesized on ribosomes in the rough endoplasmic reticulum.…”

Section: Discussionmentioning

confidence: 99%

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Nonsecreted Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Can Induce Apoptosis in Human Prostate Cancer Cells by IGF-independent Mechanisms without Being Concentrated in the Nucleus

Bhattacharyya

Pechhold

Shahjee

et al. 2006

Journal of Biological Chemistry

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Insulin-like growth factor binding protein-3 (IGFBP-3), a secreted protein, has the intrinsic ability to induce apoptosis directly without binding insulin-like growth factors. Previous studies suggested that IGFBP-3 must be secreted to exert its biological functions. IGFBP-3 contains a nuclear localization signal (NLS), and exogenous IGFBP-3 is translocated into the nucleus, suggesting that both secretion and nuclear localization may play important roles in IGFBP-3 action. To address these questions, we fused yellow fluorescent protein (YFP) to mature IGFBP-3 lacking its signal peptide so that it would remain intracellular and mutated the C-terminal NLS of IGFBP-3, 228 KGRKR 232 , to MDGEA. Following transfection of PC-3 human prostate cancer cells with these constructs, Western blots indicated that YFP-IGFBP-3 lacking a signal peptide was cell-associated and not present in the extracellular media. Moreover, the fusion protein was not N-glycosylated, indicating that it had not entered the secretory pathway. Confocal imaging showed that intracellular YFP-MDGEA-IGFBP-3 was predominantly cytoplasmic. Transient transfection of nonsecreted YFP-wild-type IGFBP-3 decreased cell viability, as assessed by staining with annexin V followed by flow cytometry. Induction of cell death was caspase-dependent, indicative of apoptosis. Apoptosis also was induced by the nonsecreted NLS mutant (YFP-MD-GEA-IGFBP-3) alone and when the IGF-binding site also had been mutated. These results indicate that IGFBP-3 can induce apoptosis in an IGF-independent manner without being secreted or concentrated in the nucleus.

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Section: Discussionmentioning

confidence: 99%

“…IGFBP-3 activates several signal transduction pathways (reviewed in Ref. 43), but a functional role only has been demonstrated for Stat1 (signal transducer and activator of transcription 1), which is required for IGFBP-3-induced apoptosis in rat chondroprogenitor cells (38).…”

mentioning

confidence: 99%

Nonsecreted Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Can Induce Apoptosis in Human Prostate Cancer Cells by IGF-independent Mechanisms without Being Concentrated in the Nucleus

Bhattacharyya

Pechhold

Shahjee

et al. 2006

Journal of Biological Chemistry

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“…In addition, integrins coopt GFR signaling pathways by directly acting on downstream components of the pathways via enzymatic actions of proteins recruited to integrin cytoplasmic tails. Finally, a different form of cross talk involves integrins interacting with extracellular GFs (Hutchings et al 2003;Vlahakis et al 2007), GF binding proteins (Munger et al 1998;Ricort 2004), and soluble GFR (Soro et al 2008).…”

Section: Cross Talk Between Integrins and Growth Factorsmentioning

confidence: 99%

Cross Talk among TGF- Signaling Pathways, Integrins, and the Extracellular Matrix

Munger¹,

Sheppard²

2011

Cold Spring Harbor Perspectives in Biology

309

275

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The growth factor TGF-b is secreted in a latent complex consisting of three proteins: TGF-b, an inhibitor (latency-associated protein, LAP, which is derived from the TGF-b propeptide) and an ECM-binding protein (one of the latent TGF-b binding proteins, or LTBPs). LTBPs interact with fibrillins and other ECM components and thus function to localize latent TGF-b in the ECM. LAP contains an integrin-binding site (RGD), and several RGD-binding integrins are able to activate latent TGF-b through binding this site. Mutant mice defective in integrin-mediated activators, and humans and mice with fibrillin gene mutations, show the critical role of ECM and integrins in regulating TGF-b signaling.

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“…Internalisation of IGFBP3 is dependent on binding to either caveolae (Lee et al, 2004;Singh et al, 2004) shown to be controlled by importin-p (Schedlich et al, 2000). The functions of these binding proteins on translocation to the nucleus are not well characterised but appear to involve regulation o f transcription and therefore could lead to IGFBP dependent cellular effects such as apoptosis (Ricort, 2004). …”

Section: Igfbp3 Andmentioning

confidence: 99%

Novel strategies for enhancing tissue integration in cartilage repair

Davies

Caterson

Duance

2004

Int J Experimental Path

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Introduction Articular cartilage is unable to initiate a spontaneous repair response when injured due to its avascular and aneural properties. Within adult cartilage, chondrocytes are entrapped within an extensive extracellular matrix and are unable to migrate to sights of injury to regulate tissue repair. Injury to this tissue therefore inevitably leads to degeneration of the cartilage and the development of degenerative diseases such as osteoarthritis. The surgical technique of autologous chondrocyte transplantation (ACT) was developed for the treatment of full‐thickness cartilage defects (Brittberg et al. 1994). Implantation of chondrocytes into the defect site repairs the injury site with a mixture of fibrocartilaginous and hyaline‐like tissue that poorly integrates with the existing cartilage and frequently degenerates with time. In this current study, we have developed an in vitro model to investigate methods for enhancing this integration and the development of a more biomechanically stable repair tissue. Materials and methods Bovine articular cartilage explants from the metacarpalphalangeal joint were experimentally injured using a stainless steel trephine and cultured for a period of 28 days. Autologous chondrocytes in an agarose suspension were injected into the interface region at the injury site. Media was collected and analysed for proteoglycan and collagen content using the DMMB and hydroxyproline assays, respectively. Matrix metalloproteinase (MMP) expression was also analysed using zymography and an adapted collagen fibril assay. Results Morphological analyses indicate attempts at repair and integration within both control and experimental treatment groups, although the presence of autologous chondrocytes appeared to amplify this repair response. Although not statistically significant, considerable differences in proteoglycan release between injured explants and the intact control group were seen. Collagen release into the media was only seen at day 28 within experimental cultures. An up‐regulation of MMP‐2 and MMP‐9 was seen within the experimental cultures compared to the controls. Preliminary data also suggest up‐regulation of collagenases in the experimental group when compared to controls. Discussion As seen with clinical ACT treatment, the presence of autologous chondrocytes appears to enhance repair and integration attempts; however, morphologically, this repair tissue appears to be fibrocartilaginous. Further analysis will establish whether the repair tissue is true hyaline cartilage and monitor the synthesis and turnover of macromolecules within the established culture system.

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Insulin-like growth factor binding protein (IGFBP) signalling

Cited by 49 publications

References 64 publications

Nonsecreted Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Can Induce Apoptosis in Human Prostate Cancer Cells by IGF-independent Mechanisms without Being Concentrated in the Nucleus

Nonsecreted Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Can Induce Apoptosis in Human Prostate Cancer Cells by IGF-independent Mechanisms without Being Concentrated in the Nucleus

Cross Talk among TGF- Signaling Pathways, Integrins, and the Extracellular Matrix

Novel strategies for enhancing tissue integration in cartilage repair

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