Chapter 71 - Mitogen-Activated Protein Kinases

Abstract

The MAPK family is involved in a broad range of cellular responses and has been implicated in a number of human pathologies. While the core components of the system are simply protein kinases, the mechanisms in which they affect a cellular response are diverse. In mammals, there are three major and distinct MAPK modules: extracellular regulated kinase (ERK), SAPK/JNK, and p38 MAPK. There is potentially a fourth module, ERK5, but the relative dearth of tools and reagents has left this potential module less well characterized. MAPKs are not just links that passively hand-off the message they receive to the next component in the system. Timing, localization, activity, and cross-regulation all affect the final outcome, and this often determines the fate of the cell through changes in transcription, protein synthesis, and survival. The core MAPK pathway components are often adapted through the use of localization scaffolds, and sequestered into proximity with other molecules to allow preferential or selective activation of specific targets. The p38 MAPK pathway also responds to various stress stimuli, including lipopolysaccharide (LPS) and inflammatory cytokines, and is sometimes known as SAPK2. In addition to inflammation and stress, p38 also plays a role in skeletal muscle differentiation. Due to its strong linkage to inflammation, significant effort has been made to determine the role of p38 in rheumatoid arthritis (RA) and inflammatory pulmonary disease.