Rat liver cytosol contains an inhibitor of the casein kinases 1 and 2 from the same source

Cyclic AMP-independent casein kinases are present in a variety of mammalian tissues, including rabbit muscle [l-3] and reticulocytes [4], pig leucocytes [5], bovine adrenal cortex [6], rat liver nuclei [7] and cytosol [8,9]. Each one of these tissues contains two types of casein kinases which can be tentatively classified according to their molecular weights: type I has M, 34 000-42 000; type II has Mr 123 000-l 90 000. These two types of enzymes are also different in their kinetic properties. An important characteristic of both types of enzymes from rabbit muscle, pig leucocytes and rat liver cytosol is that they phosphorylate and inactivate I-form glycogen synthase in a cyclic AMPand Ca*+-independent manner. However, the effects promoted by the type I enzymes are greater than those promoted by the type II. Whether or not these kinases are regulated by intracellular modulators is still unknown. In [ lo,1 l] a heat-stable protein inhibitor of the G-type (type II) casein kinase has been described in adrenal cortex, which was inactive on the A-type (type I) enzyme from the same tissue. The presence of a protein inhibitor has also been reported in rat liver nuclei [ 121. The latter inhibits only the casein kinases of nuclear origin, being inactive on the cytosolic enzymes. Here we report a heat-labile inhibitor in rat liver cytosol, of both cytosolic casein kinase 1 (CK-1 or type I) and 2 (CK-2 or type II) from the same tissue. The inhibiting effect was not due to ATPase, protein phosphatase or protease activity. The possible role of this inhibitor in the physiological regulation of the cytosolic casein kinases is discussed.