Regulation of cell proliferation and survival: convergence of protein kinases and caspases

Abstract

Intricate networks of protein kinases are intimately involved in the regulation of cellular events related to cell proliferation and survival. In addition to protein kinases, cells also contain networks of proteases including aspartic-acid directed caspases organized in cascades that play a major role in the regulation of cell survival through their involvement in the initiation and execution phases of apoptosis. Perturbations in regulatory protein kinase and caspase networks induce alterations in cell survival and frequently accompany transformation and tumorigenesis. Furthermore, recent studies have documented that caspases or their substrates are subject to phosphorylation in cells illustrating a potential convergence of protein kinase and caspase signaling pathways. Interestingly, a number of caspase substrates are protected from cleavage when they are phosphorylated at sites that are adjacent to caspase cleavage sites. While it is theoretically possible that many distinct protein kinases could protect proteins from caspase-mediated cleavage, protein kinase CK2 is of particular interest because acidic amino acids, including aspartic acid residues that are recognized by caspases, are its dominant specificity determinants.