Sensitivity and specificity amplification in signal transduction.
Intracellular signal transduction pathways transmit signals from the cell surface to various intracellular destinations, such as cytoskeleton and nucleus through a cascade of protein-protein interactions and activation events, leading to phenotypic changes such as cell proliferation, differentiation, and death. Over the past two decades, numerous signaling proteins and signal transduction pathways have been discovered and characterized. There are two major classes of signaling proteins: phosphoproteins (e.g., mitogen-activated protein kinases) and guanosine triphosphatases (GTPases; e.g., Ras and G proteins). They both function as molecular switches by addition and removal of one or more high-energy phosphate groups. This review discusses developments that seek to quantify the signal transduction processes with kinetic analysis and mathematical modeling of the signaling phosphoproteins and GTPases. These studies have provided insights into the sensitivity and specificity amplification of biological signals in integrated systems.
Li
Guangpu
G
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. guangpu-li@ouhsc.edu
Qian
Hong
H
D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology*
D034521:Nuclear Matrix-Associated Proteins; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D020558:GTP Phosphohydrolases