TGF-beta 1 modulation of IGF-I signaling pathway in rat thyroid epithelial cells.
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.
Mincione
Gabriella
G
Dipartimento di Oncologia e Neuroscienze, Facoltà di Medicina e Chirurgia, Università G. D'Annunzio, Via dei Vestini, 31, Chieti, Italy. g.mincione@unich.it
Esposito
Diana L
DL
Di Marcantonio
Maria Carmela
MC
Piccirelli
Alessandro
A
Cama
Alessandro
A
Colletta
Giulia
G
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D050737:Proto-Oncogene Proteins c-crk; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D013961:Thyroid Gland; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
C493872:Crk protein, rat; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D016212:Transforming Growth Factor beta; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D020928:Mitogen-Activated Protein Kinases