Signal Transduction in Thyrocyte
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The most important and well-known signaling pathway in thyrocytes is the thyroid stimulating hormone (TSH) receptor-mediated signal transduction. Once TSH binds to the TSH receptor, the activation of adenylate cyclase system stimulates thyrocyte growth, and activation of the phospholipase C system induces thyroid hormone biosynthesis. However, beyond these classical signaling pathways, TSH can also induce tyrosine phosphorylation of various proteins, even though the TSH receptor itself is not a tyrosine kinase. Our study showed that TSH could induce tyrosine phosphorylation of signal transducer and activator of transcription by activating an unknown tyrosine kinase and increase tyrosine phosphorylation of the 66Shc protein by upregulating the expression of Shc protein. We also attempted to identify a 120 kDa phosphoprotein, the most prominent tyrosine phosphoprotein observed when thyrocytes were stimulated by TSH. Through high-performance liquid chromatography (HPLC) and anti-phosphotyrosine immunoblotting, we identified the 120 kDa protein as Eg5, a kinesin protein important in cell division. Scavenging reactive oxygen species (ROS) is very important in thyrocytes. To synthesize thyroid hormone, thyrocytes must generate hydrogen peroxide to oxidize iodine molecules. If hydrogen peroxide and ROS induced by hydrogen peroxide are not effectively controlled, they can damage proteins and DNA in the thyrocyte. Understanding the precise mechanisms of the ROS scavenging system is crucial because it may be associated with the high incidence of autoimmune thyroid diseases and thyroid cancers. Continued efforts to elucidate the biochemical reactions within thyrocytes are necessary to understand the normal physiology of the thyroid and the underlying pathologic processes.
Abstract
The most important and well-known signaling pathway in thyrocytes is the thyroid stimulating hormone (TSH) receptor-mediated signal transduction. Once TSH binds to the TSH receptor, the activation of adenylate cyclase system stimulates thyrocyte growth, and activation of the phospholipase C system induces thyroid hormone biosynthesis. However, beyond these classical signaling pathways, TSH can also induce tyrosine phosphorylation of various proteins, even though the TSH receptor itself is not a tyrosine kinase. Our study showed that TSH could induce tyrosine phosphorylation of signal transducer and activator of transcription by activating an unknown tyrosine kinase and increase tyrosine phosphorylation of the 66Shc protein by upregulating the expression of Shc protein. We also attempted to identify a 120 kDa phosphoprotein, the most prominent tyrosine phosphoprotein observed when thyrocytes were stimulated by TSH. Through high-performance liquid chromatography (HPLC) and anti-phosphotyrosine immunoblotting, we identified the 120 kDa protein as Eg5, a kinesin protein important in cell division. Scavenging reactive oxygen species (ROS) is very important in thyrocytes. To synthesize thyroid hormone, thyrocytes must generate hydrogen peroxide to oxidize iodine molecules. If hydrogen peroxide and ROS induced by hydrogen peroxide are not effectively controlled, they can damage proteins and DNA in the thyrocyte. Understanding the precise mechanisms of the ROS scavenging system is crucial because it may be associated with the high incidence of autoimmune thyroid diseases and thyroid cancers. Continued efforts to elucidate the biochemical reactions within thyrocytes are necessary to understand the normal physiology of the thyroid and the underlying pathologic processes.