Characterization of an histone kinase activity specifically found in hyperfunctioning benign thyroid tumors

Abstract

We previously found that human hyperfunctioning benign thyroid tumors contained a histone kinase activity not found in the normal human thyroid gland (peak IV), as revealed by DE 52 cellulose chromatography (Biochem. Biophys. Res. Commun., 89, 1314, 1979). Peak IV histone kinase activity partially coeluted with a phosvitin kinase activity, which in contrast was also observed in normal tissue. o 1. Peak IV histone kinase activity is different from that of types I and II cAMP-dependent histone kinases, since: a) its activity was not modified by the specific thermostable inhibitor of the cAMP-dependent protein kinases, b) this activity was not enhanced by cAMP up to 10 −4 M, c) its enzymatic characteristics were different from those of peaks I and II: K m for histone = 9.5 g/ml vs 100 g/ml; K m for ATP = 3.8 × 10 −6 M vs 2.2 × 10 −5 M (values for peak IV and peaks I + II, respectively) and d) increasing amounts of NaCl, up to 250 mM, enhanced peak IV histone kinase activity, while that of peaks I and II was decreased. 2. The enzymatic properties of peak IV histone kinase activity are different from those of peak IV phosvitin kinase activity: a) K m for ATP = 3.8 × 10 −6 M vs 2.5 × 10 −5 M; Mg 2+ requirement for maximum activation: 10 mM and 4 mM (values for histone kinase and phosvitin kinase, respectively), b) increasing the concentration of PO 4 3−, up to 80 mM, inhibited histone kinase activity, while phosvitin kinase was increased. In conclusion, human hyperfunctioning benign thyroid tumors contain a cAMP-independent histone kinase activity not found in normal tissue, different from types I and II and from an associated normal phosvitin kinase activity.