Protein tyrosine phosphatase-eta expression is upregulated by the PKA-dependent and is downregulated by the PKC-dependent pathways in thyroid cells.
We have recently reported the isolation of a rat cDNA encoding a receptor-type tyrosine phosphatase, which appears to be a marker of thyroid differentiation. To elucidate the molecular mechanisms underlying r-PTPeta expression in normal thyroid cells both in vitro and in vivo, we investigated the regulation of r-PTPeta expression in cultured thyrocytes (the rat cell line PC Cl 3) and in an animal model of TSH-dependent thyroid goitrogenesis. In vitro studies showed that mRNA expression of r-PTPeta in thyroid cells is induced in a time- and dose-dependent manner by the activation of growth- and differentiation-linked PKA pathways (TSH and forskolin), whereas it is down-regulated by the activation of the proliferative dedifferentiating PKC-dependent transduction pathway (TPA). However, the regulation of r-PTPeta expression by TSH and TPA, respectively, is observed only in normal thyroid cells, but is lost in transformed thyroid cells. In vivo studies with thiouracil-fed rats demonstrated that increased serum levels of TSH up-regulated r-PTPeta mRNA expression in parallel with the stimulation of thyroid growth and function. The reduction of blood TSH levels due to iodide refeeding to goitrous rats determined a marked down-regulation of r-PTPeta expression, in parallel with involution of thyroid hyperplasia. Taken together these results demonstrate that the phosphatase r-PTPeta is regulated by the two main thyroid regulatory pathways and suggest that it may play an important role in the growth and differentiation of thyroid cells.
Martelli
M L
ML
Facoltà di Medicina e Chirurgia di Catanzaro, Università degli Studi di Reggio Calabria, via Tommaso Campanella 5, Catanzaro, 88100, Italy.
Trapasso
F
F
Bruni
P
P
Berlingieri
M T
MT
Battaglia
C
C
Vento
M T
MT
Belletti
B
B
Iuliano
R
R
Santoro
M
M
Viglietto
G
G
Fusco
A
A
D000818:Animals; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects; D007454:Iodides / Q000494:pharmacology; D008934:Mitogens / Q000378:metabolism / Q000494:pharmacology; D011441:Propylthiouracil / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction; D013961:Thyroid Gland / Q000166:cytology; D013972:Thyrotropin / Q000494:pharmacology; D015854:Up-Regulation
D007454:Iodides; D008934:Mitogens; D011441:Propylthiouracil; D013972:Thyrotropin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D017027:Protein Tyrosine Phosphatases