Intracellular transport mechanisms of signal transducers.
Recent discoveries have revolutionized our conceptions of enzyme-substrate specificity in signal transduction pathways. Protein kinases A and C are localized to discreet subcellular regions, and this localization changes in an isozyme-specific manner upon activation, a process referred to as translocation. The mechanisms for translocation involve interactions of soluble kinases with membrane-bound anchor proteins that recognize individual kinase isoenzymes and their state of activation. Recently, modulation of kinase-anchor protein interactions has been used to specifically regulate, positively or negatively, the activity of C kinase isozymes. Also described in this review is a role for the Rab family of small G proteins in regulating subcellular protein trafficking. The pathophysiological significance of disrupted subcellular protein transport in cell signaling and the potential therapeutic utility of targeted regulation of these events are in the process of being characterized.
Dorn
Gerald W
GW
Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0542, USA. dorngw@ucmail.uc.edu
Mochly-Rosen
Daria
D
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000502:physiology
D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020691:rab GTP-Binding Proteins