A kinetic model for calcium dynamics in RAW 264.7 cells: 2. Knockdown response and long-term response.
This article addresses how quantitative models such as the one proposed in the companion article can be used to study cellular network perturbations such as knockdowns and pharmacological perturbations in a predictive manner. Using the kinetic model for cytosolic calcium dynamics in RAW 264.7 cells developed in the companion article, the calcium response to complement 5a (C5a) for the knockdown of seven proteins (C5a receptor; G-beta-2; G-alpha,i-2,3; regulator of G-protein signaling-10; G-protein coupled receptor kinase-2; phospholipase C beta-3; arrestin) is predicted and validated against the data from the Alliance for Cellular Signaling. The knockdown responses provide insights into how altered expressions of important proteins in disease states result in intermediate measurable phenotypes. Long-term response and long-term dose response have also been predicted, providing insights into how the receptor desensitization, internalization, and recycle result in tolerance. Sensitivity analysis of long-term response shows that the mechanisms and parameters in the receptor recycle path are important for long-term calcium dynamics.
Maurya
Mano Ram
MR
Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA.
Subramaniam
Shankar
S
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000502:physiology; D007700:Kinetics; D008264:Macrophages; D051379:Mice; D008954:Models, Biological; D044087:Receptor, Anaphylatoxin C5a / Q000172:deficiency / Q000502:physiology; D015398:Signal Transduction
D044087:Receptor, Anaphylatoxin C5a; D019204:GTP-Binding Proteins; D002118:Calcium