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OVEREXPRESSION OF THE TYPE II TRANSFORMING GROWTH FACTOR‐β RECEPTOR INHIBITS FIBROBLAST PROLIFERATION AND ACTIVATES EXTRACELLULAR SIGNAL REGULATED KINASE AND C‐JUN N‐TERMINAL KINASE
Author(s) -
Goldberg Howard J.,
Huszár Tamás,
Mózes Miklós M.,
Rosivall László,
Mucsi István
Publication year - 2002
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1006/cbir.2001.0832
Subject(s) - platelet derived growth factor receptor , mapk/erk pathway , microbiology and biotechnology , tgf beta receptor 2 , growth factor receptor , platelet derived growth factor , signal transduction , receptor , transforming growth factor beta , transforming growth factor , biology , chemistry , growth factor , tgf alpha , biochemistry
Transforming growth factor‐β (TGF‐β) is a bimodal regulator of cellular growth. The cellular effects of TGF‐β depend on the intensity of signals emanating from TGF‐β 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‐β receptors in NIH 3T3 fibroblasts. Overexpressed type II TGF‐β receptors suppressed fibroblast proliferation elicited by TGF‐β1, 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 α‐, but not PDGF β‐receptor protein levels were reduced by type II TGF‐β receptor overexpression. In conclusion, our system is an excellent tool to study the molecular mechanisms of growth inhibition by TGF‐β in fibroblasts. Activation of JNK and ERK, or modulation of PDGF receptor expression may be involved in this process.