Replication potential of cells via the protein kinase C-MAPK pathway: Application of a mathematical model

A mechanistically based mathematical model is used to investigate some of the important factors in priming hepatocytes to enter the G(1) phase of the cell cycle. The considers all of the relevant biochemical mechanisms from signal-receptor binding to the elevation of AP-1(activation protein transcription factor) levels. Focus is centered on the chain of biochemical events governing the sequential activation of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and AP-1. Factors such as amplitude and duration of growth factors signals, the kinetics of guanosine diphosphate (GDP) to guanosine triphosphate (GTP) conversion, and the negative feedback control mechanisms governing initial steps in cellular replication were theoretically examined. The results of our theoretical assessments support the finding that specific mutations along the PKC-API pathways can have a critical effect on the rate at which cells enter the division cycle. (C) 1999 Society for Mathematical Biology.