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-t ype tyrosine phosphatase, which appears to be a marker of thyroid different iation. To elucidate the molecular mechanisms underlying r-PTP eta expressi on in normal thyroid cells both in vitro and in vivo we investigated the re gulation of r-PTP eta 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-PTP eta in thyroid cells is induced in a time- and dose-dependent manner by the activation of growth- a nd differentiation-linked PKA pathways (TSH and forskolin), whereas it is d own-regulated by the activation of the proliferative dedifferentiating PKC- dependent transduction pathway (TPA). However, the regulation of r-PTP eta expression by TSH and TPA, respectively, is observed only in normal thyroid cells, but is lost in transformed thyroid cells. In vivo studies with thio uracil-fed rats demonstrated that increased serum levels of TSH up-regulate d r-PTP eta mRNA expression in parallel with the stimulation of thyroid gro wth and function. The reduction of blood TSH levels due to iodide refeeding to goitrous rats determined a marked down-regulation of r-PTP eta expressi on, in parallel with involution of thyroid hyperplasia. Taken together thes e results demonstrate that the phosphatase r-PTP eta is regulated by the tw o main thyroid regulatory pathways and suggest that it may play an importan t role in the growth and differentiation of thyroid cells. (C) 1998 Academi c Press.