Protein kinase signal transmission and specificity

18 March 2011

Lee Bardwell
Department of Developmental and Cell Biology
University of California, Irvine

Abstract

Signal transduction networks do much more than simply transmit a signal from the cell surface to the nucleus and other cellular targets. They transform input into output in elaborate ways, and maintain specificity from signal to cellular response despite extensive interconnections between pathways. I will discuss two or three of the following topics related to these issues:

1. Mathematical models of specificity in signal transduction: I will introduce a framework for the analysis of networks containing two or more interconnected signaling pathways, and use this framework to explore the behavior of insulating mechanisms that are thought to promote specificity in biological signaling networks.
2. Kinetic Hysteresis: My student Lamar Blackwell and I reconstituted a MAP kinase-substrate-phosphatase module in vitro with purified components and explored its behavior. We observed a phenomenon that we dubbed kinetic hysteresis, in which the characteristic time to reach steady state for the going up reaction was significantly faster than that for the coming down reaction. In the context of cellular signaling, kinetic hysteresis of this sort would enable the MAPK to respond rapidly to a transient stimulus, yet remain on well after the stimulus was removed. I will discuss our current theoretical understanding of this phenomenon.
3. Ultrasensitivity and kinase cascades: I will present a simple analytical demonstration that apparent Hill coefficients increase super-multiplicatively through a multisite phosphorylation cascade.