Identification of the thyroid transcription factor-1 as a target for rat MST2 kinase.
Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing transcription factor that is required for thyroid-specific expression of the thyroglobulin and thyroperoxidase genes as well as for lung-specific expression of the surfactant protein A, B, and C and the CC10 and the HNF-3 alpha genes. TTF-1 is a phosphoprotein, and the phosphorylation of TTF-1 has been studied already. However, the kinase(s) that could be responsible for this phosphorylation have not been known. In this paper we report the identification by in-gel kinase assay of a 56-kDa serine/threonine kinase that is able to phosphorylate TTF-1 in thyroid cells. The cloning of this kinase revealed that we had identified the rat homolog of the human MST2 kinase. The pathway in which human MST2 functions is not known; however, it does not appear to involve either mitogen-activated protein kinases such as Erk1 and Erk2 nor the stress-activated protein kinases such as JNK and p38. We show that the activity responsible for TTF-1 phosphorylation is constitutive in thyroid cells. Furthermore, we demonstrate that TTF-1 is phosphorylated in vivo by rMST2 at the same residues that had been identified previously as the major phosphorylation sites. Thus, TTF-1 represents the first identified target of this class of protein kinases.
Aurisicchio
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Stazione Zoologica A. Dohrn, Napoli, Italy.
Di Lauro
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Zannini
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D000090742:Serine-Threonine Kinase 3; D013961:Thyroid Gland / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*; D000099317:Hippo Kinases
D018398:Homeodomain Proteins; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C000614412:NKX2-1 protein, human; C000614416:Nkx2-1 protein, rat; C490817:Stk3 protein, rat; D000099317:Hippo Kinases; C097835:STK3 protein, human