LRP‐1/TβR‐V mediates TGF‐β1‐induced growth inhibition in CHO cells

Tseng, Wen-Fang; Huang, Shuan Shian; Huang, Jung San

doi:10.1016/s0014-5793(04)00185-1

Cited by 53 publications

(74 citation statements)

References 47 publications

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“…Indeed, we found that PDGF treatment of MEFs resulted in an enhancement of cell growth while having no effect on the growth of LRP1-deficient cells. Recently, LRP1 was shown to be required for the growth inhibitor properties of transforming growth factor-␤ in mink lung epithelial cells (Mv1Lu cells) (15) and Chinese hamster ovary cells (16), suggesting that LRP1 has the potential to modulate multiple signaling pathways affecting cellular growth. Further investigations are required to reveal if LRP1 provides cross-talk with other signaling pathways to fine-tune highly regulated cell proliferation, migration, and survival.…”

Section: Lrp1 Modulates Pdgfr-␤ Signalingmentioning

confidence: 99%

“…Targeted deletion of the LRP1 gene in vascular smooth muscle cells causes PDGFR overexpression and excessive activation of this signaling pathway resulting in proliferation of vascular smooth muscle cells and increased susceptibility to the development of atherosclerosis (12). The mechanism by which LRP1 affects PDGF signaling pathway is poorly understood but may involve the ability of LRP1 to regulate the transforming growth factor-␤ signaling pathway (15)(16)(17).…”

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confidence: 99%

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Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Forms a Signaling Complex with Platelet-derived Growth Factor Receptor-β in Endosomes and Regulates Activation of the MAPK Pathway

Muratoglu

Mikhailenko

Newton

et al. 2010

Journal of Biological Chemistry

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In addition to its endocytic function, the low density lipoprotein receptor-related protein 1 (LRP1) also contributes to cell signaling events. In the current study, the potential of LRP1 to modulate the platelet-derived growth factor (PDGF) signaling pathway was investigated. PDGF is a key regulator of cell migration and proliferation and mediates the tyrosine phosphorylation of LRP1 within its cytoplasmic domain. In WI-38 fibroblasts, PDGF-mediated LRP1 tyrosine phosphorylation occurred at 37°C but not at 4°C, where endocytosis is minimized. Furthermore, blockade of endocytosis with the dynamin inhibitor, dynasore, also prevented PDGFmediated LRP1 tyrosine phosphorylation. Immunofluorescence studies revealed co-localization of LRP1 with the PDGF receptor after PDGF treatment within endosomal compartments, whereas surface biotinylation experiments confirmed that phosphorylated LRP1 primarily originates from intracellular compartments. Together, the data reveal the association of these two receptors in endosomal compartments where they form a signaling complex. To study the contribution of LRP1 to PDGF signaling, we used mouse embryonic fibroblasts genetically deficient in LRP1 and identified phenotypic changes in these cell lines in response to PDGF stimulation by performing phospho-site profiling. Of 38 phosphorylated proteins analyzed, 8 were significantly different in LRP1 deficient fibroblasts and were restored when LRP1 was expressed back in these cells. Importantly, the results revealed that LRP1 expression is necessary for PDGF-mediated activation of ERK. Overall, the studies reveal that LRP1 associates with the PDGF receptor in endosomal compartments and modulates its signaling properties affecting the MAPK and Akt/phosphatidylinositol 3-kinase pathways.

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Section: Lrp1 Modulates Pdgfr-␤ Signalingmentioning

confidence: 99%

mentioning

confidence: 99%

Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Forms a Signaling Complex with Platelet-derived Growth Factor Receptor-β in Endosomes and Regulates Activation of the MAPK Pathway

Muratoglu

Mikhailenko

Newton

et al. 2010

Journal of Biological Chemistry

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“…Regulation of TGF b1 translation can also be used to control cell growth as it is a potent growth inhibitor (Schuster and Krieglstein 2002) and experiments have shown that targeting the TGF b1 receptor in CHO cells can attenuate the growth inhibitory response to TGF b1 in wild-type CHO cells (Tseng et al 2004).…”

Section: Mirna Targets Regulating Apoptosismentioning

confidence: 99%

MicroRNAs: recently discovered key regulators of proliferation and apoptosis in animal cells

Gammell

2007

Cytotechnology

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The relatively recent discovery of miRNAs has added a completely new dimension to the study of the regulation of gene expression. The mechanism of action of miRNAs, the conservation between diverse species and the fact that each miRNA can regulate a number of targets and phenotypes clearly indicates the importance of these molecules. In this review the current state of knowledge relating to miRNA expression and gene regulation is presented, outlining the key morphological and biochemical features controlled by miRNAs with particular emphasis on the key phenotypes that impact on cell growth in bioreactors, namely proliferation and apoptosis.

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“…The type V receptor (TGF-␤-RV) was shown to be identical to the low density lipoprotein receptor-related protein-1 (LRP1) (33). LRP1 has been shown to affect the signaling of TGF-␤ in Chinese hamster ovary (CHO) cells, where LRP1-deficient CHO cells gained resistance toward TGF-␤-induced cell growth arrest (34). Many other groups have also demonstrated the importance of LRP1 in TGF-␤ signaling events (35)(36)(37)(38)(39).…”

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confidence: 99%

Engulfment Protein GULP Is Regulator of Transforming Growth Factor-β Response in Ovarian Cells

Cheng

Martin

et al. 2012

Journal of Biological Chemistry

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Background:The low density lipoprotein receptor-related protein 1 (LRP1) is a transforming growth factor ␤ (TGF-␤) receptor in ovarian cells. Results: GULP is an adapter to LRP1 and mediates TGF-␤ signaling in signaling-competent early endosomes. Conclusion: GULP positively regulates TGF-␤ signaling in ovarian cells. Significance: GULP is poorly expressed in ovarian cancer cells and is a target for TGF-␤-mediated growth inhibition.

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LRP‐1/TβR‐V mediates TGF‐β1‐induced growth inhibition in CHO cells

Cited by 53 publications

References 47 publications

Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Forms a Signaling Complex with Platelet-derived Growth Factor Receptor-β in Endosomes and Regulates Activation of the MAPK Pathway

Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Forms a Signaling Complex with Platelet-derived Growth Factor Receptor-β in Endosomes and Regulates Activation of the MAPK Pathway

MicroRNAs: recently discovered key regulators of proliferation and apoptosis in animal cells

Engulfment Protein GULP Is Regulator of Transforming Growth Factor-β Response in Ovarian Cells

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