gms | German Medical Science

Figure

Figure 13: The stress activated protein-kinase path

SAP kinases are a group of cytosolic protein kinases activated in a cascade like fashion following cellular stress exposure. Their activation occurs basically via 4 mechanisms. Proimflammatory cytokines and growth factors activate SAP-kinases via interconnections with their main intracellular pathways mediated by small GTP binding proteins such as Rac1 or Cdc42. Extracellular stressors cause the generations of cermides in the within the cellular lipid membrane, which activate SAP-kinases as second messengers. DNA damage activates the tyrosinkinase c-Abl, which activates SAP-kinases via intermediary steps. Intracellular ROS denature phosphatases and thus interfere with the inactivation of SAP-kinases. In addition, ROS activate the transcriptionfactor NF-κB by mechanisms not yet understood. Activation of SAP kinases in turn activates several transcription factors, which then translocate into the nucleus. Here they activates genes coding for proteins involved in cell division, apoptosis, cytoskeleton, cell activity and inflammation. In addition, SAP-kinases activate phsopholipase A2 thus altering the release of prostaglandins and leukotrienes. Heat shock proteins belong to the chaperones, which repair denatured proteins (resoration of their three-dimensional structure). Heat skock proteins serve as an indicator for cellular stress.