Figure 2

Example of a phosphorylated protein kinase. The location of phosphorylated Ser-279 in the protein structure of human MAP kinase p38beta (p38B) is shown in this figure. A model for phosphorylated serine was located in the structural position of residue Ser-279 in the 3D crystallographic coordinates of p38B (Protein Data Bank code: 3GC8). Position of the ATP binding site is indicated. Plot was generated using PyMOL (DeLano Scientific, San Carlos, CA). The p38 pathway is one of the mitogen-activated protein kinase (MAPK) signalling cascades along with the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways. Similar to other MAPK pathways, the p38 signalling cascade involves sequential activation of MAPK kinases (MAP3Ks) and MAPK kinases (MKKs) including MKK3, MKK4, and MKK6, which directly activate p38 through phosphorylation in a cell-type- and stimulus-dependent manner. Once activated, p38 MAPKs phosphorylate serine/threonine residues on their substrates, such as transcription factors, cell cycle regulators as well as protein kinases. By the p38 signalling pathway cells can interpret a wide range of external signals, such as inflammation, hyperosmorality, UV radiation and oxidative stress and they respond appropriately by generating an excessive abundance of different biological effects.