RESUMEN
Apoptosis and the response to cell stress are evolutionary highly conserved mechanisms. Both processes require strict regulation, which is often performed by protein kinases. The mammalian Sterile 20-like kinase 1 (MST1) is a pro-apoptotic protein kinase, which is activated and cleaved by caspases upon the induction of cell stress. Being a phosphoprotein itself, the activity of MST1 is regulated by phosphorylation. Protein kinase CK2 is an anti-apoptotic protein kinase which seems to be involved in the regulation of many different cellular processes including apoptosis. There is increasing evidence that the cleavage of many substrates by caspases is regulated by phosphorylation in the close vicinity of the caspase cleavage sites. One of these kinases, implicated in the phosphorylation of caspase substrates, is protein kinase CK2. Here, we report that serine 320 of the MST1 protein is a novel phosphorylation site for the anti-apoptotic protein kinase CK2. Although serine 320 is in close vicinity to the caspase 3 cleavage site, caspase 3 cleavage of MST1 is not affected by CK2 phosphorylation. Using biochemical approaches, we were able to show that MST1 co-localizes with the CK2 subunits in the pancreatic ß-cell line INS-1 and that full-length MST1 and the activated N-terminal fragment of MST1 both interacted with the CK2 subunits in vitro and in vivo. MST1 is a basophilic kinase whereas CK2 is an acidophilic kinase. Thus, binding of these two kinases in the cytosol and in the nucleus opens the door to the phosphorylation of a variety of new substrates.
