+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Overexpression of the type II transforming growth factor-beta receptor inhibits fibroblasts proliferation and activates extracellular signal regulated kinase and c-Jun N-terminal kinase



Overexpression of the type II transforming growth factor-beta receptor inhibits fibroblasts proliferation and activates extracellular signal regulated kinase and c-Jun N-terminal kinase



Cell Biology International 26(2): 165-174



Transforming growth factor-beta (TGF-beta) is a bimodal regulator of cellular growth. The cellular effects of TGF-beta depend on the intensity of signals emanating from TGF-beta receptors. Low levels of receptor activity are sufficient to stimulate cell proliferation, while higher degrees of receptor activation are associated with growth inhibition. To study the mechanisms of these effects, a tetracycline-inducible expression system was used to overexpress type II TGF-beta receptors in NIH 3T3 fibroblasts. Overexpressed type II TGF-beta receptors suppressed fibroblast proliferation elicited by TGF-beta1, fibroblast growth factor (FGF) or platelet-derived growth factor (PDGF). Accompanying these anti-proliferative effects, increases in extracellular-signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activity were detected. Furthermore, PDGF alpha-, but not PDGF beta-receptor protein levels were reduced by type II TGF-beta receptor overexpression. In conclusion, our system is an excellent tool to study the molecular mechanisms of growth inhibition by TGF-beta in fibroblasts. Activation of JNK and ERK, or modulation of PDGF receptor expression may be involved in this process.

(PDF emailed within 0-6 h: $19.90)

Accession: 046897325

Download citation: RISBibTeXText

PMID: 11846446

DOI: 10.1006/cbir.2001.0832


Related references

Involvement of extracellular signal-regulated kinase 2 and stress-activated protein kinase/Jun N-terminal kinase activation by transforming growth factor beta in the negative growth control of breast cancer cells. Cancer Research 57(4): 628-633, 1997

cAMP inhibits transforming growth factor-beta-stimulated collagen synthesis via inhibition of extracellular signal-regulated kinase 1/2 and Smad signaling in cardiac fibroblasts. Molecular Pharmacology 70(6): 1992-2003, 2006

17-Beta-estradiol inhibits transforming growth factor-beta signaling and function in breast cancer cells via activation of extracellular signal-regulated kinase through the G protein-coupled receptor 30. Molecular Pharmacology 74(6): 1533-1543, 2008

Antisense extracellular signal-regulated kinase-2 gene therapy inhibits platelet-derived growth factor-induced proliferation, migration and transforming growth factor-beta(1) expression in vascular smooth muscle cells and attenuates transplant vasculopathy. Transplant International 21(1): 30-38, 2007

The platelet-activating factor receptor activates the extracellular signal-regulated kinase mitogen-activated protein kinase and induces proliferation of epidermal cells through an epidermal growth factor-receptor-dependent pathway. Journal of Pharmacology and Experimental Therapeutics 300(3): 1026-1035, 2002

Platelet-derived growth factor activates porcine thecal cell phosphatidylinositol-3-kinase-Akt/PKB and ras-extracellular signal-regulated kinase-1/2 kinase signaling pathways via the platelet-derived growth factor-beta receptor. Endocrinology 141(4): 1545-1553, 2000

Activation of extracellular signal-regulated kinase 1 and activator protein-1 by transforming growth factor-beta1 in mesangial cells is dependent on TGF-beta type II receptor. FASEB Journal 12(4): A165, March 17, 1998

Smad3 and extracellular signal-regulated kinase 1/2 coordinately mediate transforming growth factor-beta-induced expression of connective tissue growth factor in human fibroblasts. Journal of Investigative Dermatology 124(6): 1162-1169, 2005

Expression and activation of platelet-derived growth factor β receptor, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) in canine mammary tumours. Research in Veterinary Science 110: 29-33, 2017

Betaxolol inhibits extracellular signal-regulated kinase and P70S6 kinase activities and gene expressions of platelet-derived growth factor A-chain and transforming growth factor-beta1 in Dahl salt-sensitive hypertensive rats. Hypertension Research 25(2): 211-219, 2002

Anti-tumor peptide AP25 decreases cyclin D1 expression and inhibits MGC-803 proliferation via phospho-extracellular signal-regulated kinase-, Src-, c-Jun N-terminal kinase- and phosphoinositide 3-kinase-associated pathways. Molecular Medicine Reports 12(3): 4396-4402, 2016

Glycated albumin increases oxidative stress, activates NF-kappa B and extracellular signal-regulated kinase (ERK), and stimulates ERK-dependent transforming growth factor-beta 1 production in macrophage RAW cells. Journal of Laboratory and Clinical Medicine 141(4): 242-249, 2003

Transforming growth factor beta signaling via Ras in mesenchymal cells requires p21-activated kinase 2 for extracellular signal-regulated kinase-dependent transcriptional responses. Cancer Research 67(8): 3673-3682, 2007

Synergistic activation of extracellular signal-regulated kinase in human dermal fibroblasts by human telomerase reverse transcriptase and transforming growth factor-beta 1. Journal of Surgical Research 143(2): 415-421, 2007

Keratinocyte growth factor stimulates alveolar type II cell proliferation through the extracellular signal-regulated kinase and phosphatidylinositol 3-OH kinase pathways. American Journal of Respiratory Cell and Molecular Biology 30(6): 901-907, 2004