Activation of protein kinase CK2 by LPS is mediated by the MAP kinase pathway

Stimulation of macrophages by Gram-negative bacterial lipopolysaccharide (L PS) rapidly leads to the activation of several protein kinases and the subs equent phosphorylation of transcription factors that regulate LPS-inducible genes. Several investigators have shown that the MAP kinases (MAPKs) are r apidly activated following LPS stimulation. We previously reported that LPS stimulation also up-regulates the enzymatic activity of protein kinase CK2 , a ubiquitous serine/threonine kinase, although the signaling cascade that leads to CK2 activation in macrophages is unknown. Because MAPKs are known to be rapidly activated by LPS, we performed additional studies in order t o determine if CK2 activation was a downstream target of MAPKs. Our studies revealed that CK2 activity was rapidly and transiently up-regulated in LPS -stimulated RAW264.7 murine macrophages. We found that PD98059, an inhibito r of ERK kinase activation by the MAP kinase MEK-1, blocked LPS-induced up- regulation of CK2 activity. In contrast, the p38 kinase inhibitor SB203580 did not block CK2 activation by LPS. This finding suggests that CK2 activat ion was mediated by the ERK kinase signaling cascade, but not by the p38 ki nase cascade. We also found that LPS stimulation resulted in the rapid seri ne phosphorylation of the catalytic alpha and alpha' subunits of CK2. This contrasts with other studies using growth factor-stimulated fibroblasts in which only phosphorylation of the regulatory beta subunit of CK2 was observ ed. Thus, LPS stimulation leads to rapid activation and cell type-specific phosphorylation of CK2 in macrophages.