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TGF-beta 1 modulation of IGF-I signaling pathway in rat thyroid epithelial cells
- Source :
- Experimental cell research. 287(2)
- Publication Year :
- 2003
-
Abstract
- Transforming growth factor beta 1 (TGF-beta 1) and insulin-like growth factor I (IGF-I) have contrasting effects on cell cycle regulation in thyroid cells and TGF-beta 1 induces a dramatic decrease in IGF-I-induced cell proliferation. The aim of the present study was to investigate the molecular mechanism of cross-talk between TGF-beta 1 and IGF-I in FRTL-5 cells. TGF-beta 1 affected IGF-I-stimulated insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation and its association with Grb2 protein. Moreover, TGF-beta 1 decreased the IGF-I-induced tyrosine phosphorylation of the adaptor protein CrkII and its association with the IGF-I receptor. These results were accompanied by TGF-beta 1 inhibition of IGF-I-stimulated mitogen-activated protein kinase phosphorylation and activation. Conversely, TGF-beta 1 did not alter IGF-I-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity, IGF-I-induced tyrosine phosphorylation of Shc, and its binding to Grb2. Taken together, these findings provide a molecular basis for the growth-inhibitory action of TGF-beta 1 on the IGF-I-induced mitogenic effect.
- Subjects :
- Thyroid Gland
Protein tyrosine phosphatase
Biology
Receptor tyrosine kinase
Cell Line
chemistry.chemical_compound
Transforming Growth Factor beta
Proto-Oncogene Proteins
Animals
Protein phosphorylation
Insulin-Like Growth Factor I
Phosphorylation
Tyrosine phosphorylation
Epithelial Cells
Cell Biology
Proto-Oncogene Proteins c-crk
Receptor, Insulin
Cell biology
Rats
Enzyme Activation
chemistry
biology.protein
Cancer research
Tyrosine
GRB2
Mitogen-Activated Protein Kinases
Tyrosine kinase
Platelet-derived growth factor receptor
Cell Division
Signal Transduction
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 287
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Experimental cell research
- Accession number :
- edsair.doi.dedup.....bb2664007fe9842a33b0b72248dadda4