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Vol. 273, Issue 3, 1477-1482, January 16, 1998
From the 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
Identification of the Thyroid Transcription Factor-1 as a
Target for Rat MST2 Kinase
,¶, and¶
Stazione Zoologica "A. Dohrn,
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.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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