Human Protein Kinase CK2 Phosphorylates Matrix Metalloproteinase 2 and Inhibits its Activity

Matrix metalloproteinase 2 (MMP‐2) is involved in cancer development and is overexpressed in a variety of malignant tumors. MMP‐2 activity is controlled mainly by transcription, proteolytic activation, and inhibition by endogenous inhibitors. It had previously been demonstrated that MMP‐2 activity is also regulated by phosphorylation at several sites by protein kinase C. Here we demonstrate, by means of bioinformatics and biochemical and cellular assays, that protein kinase CK2 also acts as a modulator of MMP‐2 activity. CK2 down‐regulates MMP‐2 in vitro, and inhibition of CK2 in human fibrosarcoma cells results in up‐regulation of MMP‐2. The discovery of the crosstalk between MMP‐2 and CK2 opens the possibility of new combined anticancer therapies. Crosstalk in cancer cells: Phosphorylation mediated by protein kinase CK2 is presented as a possible regulatory mechanism for MMP‐2. In vitro phosphorylation decreases the activity of MMP‐2 towards gelatin, and TBB (4,5,6,7‐tetrabromobenzotriazole), a selective CK2 inhibitor, can abolish this effect. Inhibition of CK2 in human fibrosarcoma cells with TBB results in upregulation of MMP‐2.