Insight into intra- and inter-molecular interactions of PKC: design of specific modulators of kinase function.
Protein kinase C (PKC) is a family of kinases that are critical in many cellular events. These enzymes are activated by lipid-derived second messengers, are dependent on binding to negatively charged phospholipids and some members also require calcium to attain full activation. The interaction with lipids and calcium activators is mediated by binding to the regulatory domains C1 and C2. In addition, many protein-protein interactions between PKC and other proteins have been described. These include interactions with adaptor proteins, substrates and cytoskeletal elements. Regulation of the interactions between PKC, small molecules and other proteins is essential for signal transduction to occur. Finally, a number of auto-inhibitory intra-molecular protein-protein interactions have also been identified in PKC. This chapter focuses on mapping the sites for many of these inter- and intra-molecular interactions and how this information may be used to generate selective inhibitors and activators of PKC signaling.
Kheifets
Viktoria
V
Department of Chemical and Systems Biology, Stanford University School of Medicine, CCSR, Rm 3145A, 269 Campus Drive, Stanford, CA 94305-5174, USA.
Mochly-Rosen
Daria
D
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
D010743:Phospholipids; D011493:Protein Kinase C; D002118:Calcium