Protein Tyrosine Phosphatase-η Expression Is Upregulated by the PKA-Dependent and Is Downregulated by the PKC-Dependent Pathways in Thyroid Cells

Abstract

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-PTPη expression in normal thyroid cells bothin vitroandin vivo,we investigated the regulation of r-PTPη expression in cultured thyrocytes (the rat cell line PC Cl 3) and in an animal model of TSH-dependent thyroid goitrogenesis.In vitrostudies showed that mRNA expression of r-PTPη 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-PTPη expression by TSH and TPA, respectively, is observed only in normal thyroid cells, but is lost in transformed thyroid cells.In vivostudies with thiouracil-fed rats demonstrated that increased serum levels of TSH up-regulated r-PTPη 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-PTPη expression, in parallel with involution of thyroid hyperplasia. Taken together these results demonstrate that the phosphatase r-PTPη 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.