PKC-&zgr;-associated CK2 Participates in the Turnover of Free I&kgr;B&agr;

Author： Bren G.D. Pennington K.N. Paya C.V.

ISSN： 0022-2836

Source： Journal of Molecular Biology, Vol.297, Iss.5, 2000-04, pp. : 1245-1258

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Abstract

The atypical PKC isoenzymes, &zgr; and &igr;, activate NF-&kgr;B, a mechanism thought to mediate the anti-apoptotic and proliferative features of these kinases. PKC-&zgr; has been shown to be associated with an I&kgr;B&agr; kinase in resting cells. In this study, we have sought to identify the PKC-&zgr; associated kinase and understand how PKC-&zgr; mediates basal I&kgr;B&agr; turnover in vivo. We demonstrate that the PKC-&zgr;-associated I&kgr;B&agr; kinase is CK2. This kinase, previously shown to phosphorylate the PEST domain of I&kgr;B molecules, co-precipitates with PKC-&zgr; in resting cells. In vitro, PKC-&zgr; interacts with CK2-&bgr;. The in vivo PKC-&zgr;-associated CK2 preferentially phosphorylates S293 of I&kgr;B&agr; as compared to non-associated CK2. The functional relevance of this observation is supported by the fact that the turnover of free I&kgr;B&agr; in resting cells is S293-dependent. Moreover, overexpressing PKC-&zgr; results in lower steady-state protein levels of free I&kgr;B&agr;, which is dependent on S293. Lastly, it is shown that PKC-&zgr; wt but not kinase dead leads to the in vitro phosphorylation of both CK2- and &bgr;. These studies demonstrate that the association between CK2 and PKC-&zgr; may play a major role in the control of the basal turnover of free I&kgr;B, in the absence of extracellular stimuli.