The Roles of Mammalian Mitogen-Activated Protein Kinase-Activating Protein Kinases (MAPKAPKs) in Cell Cycle Control pp.27-62
Authors: (Sergiy Kostenko, Alexey Shiryaev, Nancy Gerits, Ugo Moens - Univ. of Tromso, Faculty of Medicine, Institute of Medical Biology, Dept. of Microbiology and Virology, Tromso, Norway)
Abstract: Signal transduction pathways often modulate cell proliferation by targeting the activity of cell cycle regulating proteins. One of the signaling pathways that can control the cell cycle is the mitogen-activated protein kinase (MAPK) signaling cascade. In mammalian cells, the classical MAPK pathway consists of sequential phosphorylation events leading to activation of a MAPK kinase kinase, a MAPK kinase, and a MAPK. MAPK in turn phosphorylates non-protein kinase substrates such as transcription factors, but it can also phosphorylate yet other protein kinases, referred to as MAPK-activating protein kinases (MAPKAPK). Eleven mammalian MAPKAPKs have been identified so far; six of them belong to the group of AGC protein kinases (RSK1, RSK2, RSK3, RSK4, MSK1, and MSK2), while the other five belong to the family of calmodulin-dependent kinases (MK2, MK3, MK5, MNK1, and MNK2). In this review we will discuss those MAPKAPKs that play a role cell-cycle regulation as well as the potential use of specific MAPKAPK inhibitors as therapy in conditions with abnormal cell cycle regulation.