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Thyroid hormones differentially regulate phosphorylation of ERK and Akt via integrin α v β 3 receptor in undifferentiated and differentiated PC‐12 cells
Author(s) -
Barbakadze Tamar,
Natsvlishvili Nino,
Mikeladze David
Publication year - 2014
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3013
Subject(s) - protein kinase b , phosphorylation , mapk/erk pathway , chemistry , receptor , endocrinology , integrin , cellular differentiation , medicine , microbiology and biotechnology , biology , biochemistry , gene
The effects of 3,5,3′‐triiodo‐ l ‐thyronine (T3) and l ‐thyroxine (T4) on the integrin α v β 3 receptor of thyroid hormones (TH) were investigated in pheochromocytoma PC‐12 cells. Differentiation was induced by treatment of PC‐12 cells with fisetin and the levels of phosphorylated extracellular signal‐regulated kinase (ERK) and Akt in cytoplasm, as well as the content of FoxO6 transcription factor in nuclei was analysed in undifferentiated and differentiated conditions. We have found that in undifferentiated PC‐12 cells, tetraiodothyroacetic acid (TETRAC), a known inhibitor of binding of T4 and T3 to plasma membrane integrin α v β 3 receptor inhibits T4‐dependent phosphorylation of ERK, whereas in differentiated PC‐12 cells, TETRAC abolishes the effect of T3. In undifferentiated PC‐12 cells, both TH increase the level of p‐Akt, and this enhancement is not sensitive to TETRAC. In differentiated PC‐12 cells, both TH increase the level of p‐Akt; however, only T3‐dependent activation of Akt is sensitive to the TETRAC. Furthermore, our results have shown that in differentiated PC‐12 cells, the expression of FoxO6 was higher than in undifferentiated PC‐12 cells, and this elevation has not changed under the action of TH. Only in undifferentiated PC‐12 cells the T3‐dependent expression of FoxO6 was sensitive to the TETRAC. We propose that PC‐12 cells contain integrin α v β 3 receptor, which T3 and T3/T4 sites are differentially regulated by TH in undifferentiated and differentiated conditions. Copyright © 2013 John Wiley & Sons, Ltd.