Compartmentalised MAPK Pathways

Abstract

The mitogen-activated protein kinase (MAPK) pathway provides cells with the means to interpret external signal cues or conditions, and respond accordingly. This cascade regulates many cell functions such as differentiation, proliferation and migration. Through modulation of both the amplitude and duration of MAPK signalling, cells can control their responses to the multiple activators of the pathway. In addition, recent work has highlighted the importance of the cellular compartment from which the signalling occurs. Cells have developed intricate systems that enable them to localise MAPK components to specific subcellular domains in response to a particular stimulus. Consequently, different factors can activate the same kinase in separate locations. Crucial to this ability are molecular scaffolds, which act as signalling modules for MAPKs, confining them to the desired compartment. The participation of the MAPK network in fundamental physiological processes, such as cell proliferation and inflammation, and the derangement of the homeostasis that occurs in disease processes, renders MAPK a highly desirable target for therapeutic intervention. As we enhance our comprehension of scaffolds and other regulatory molecules, novel targets for drug design may be discovered that will afford selective and specific MAPK modulation.

Mitogen activated protein kinases: a role in inflammatory bowel disease?

“…Once stimulated, the MAPK can then bind and stimulate other kinase targets (coloured orange in Fig. 2), translocate to the nucleus to activate gene transcription or induce other actions such as cell migration [14].…”

Spatial control of Shoc2 scaffold-mediated ERK1/2 signaling requires remodeling activity of the ATPase PSMC5

“…Extensive studies of the signaling pathway mediated by extracellular signal-regulated kinases 1 and 2 (ERK1/2, also known as MAPK3 and MAPK1, respectively) have resulted in the identification of a large number of protein-protein interactions as well as multiple substrates, elucidating the complexity of the ERK1/2 pathway (Brown and Sacks, 2008;Chen et al, 2001;Katz et al, 2007). The branching of signals within the ERK1/2 pathway is regulated by scaffold proteins.…”

Histone H3 Phosphorylation (Ser10, Ser28) and Phosphoacetylation (K9S10) Are Differentially Associated with Gene Expression in Liver of Rats Treated In Vivo with Acute Ethanol

“…The activation of the MAP kinases ERK1/2 and JNK can increase the mRNA expression of c-fos and c-jun, respectively, and hence AP-1 activation (Clayton and Mahadevan, 2003). MAP kinases are implicated in alcoholic liver disease because they regulate inflammation, steatosis, apoptosis, and necrosis (Aroor and Shukla, 2004;Boutros et al, 2008;Brown and Sacks, 2008). Ethanol is known to activate AP-1 in HepG2 cells (Román et al, 1999), and chronic ethanol feeding also increases AP-1 in the liver (Wang et al, 1998).…”