When more is less: Dual phosphorylation protects signaling off-state against overexpression

Kinases in signaling pathways are commonly activated by multisite phosphorylation. For example, the mitogen-activated protein kinase Erk is activated by its kinase Mek by two consecutive phosphorylations within its activation loop. In this article, we use kinetic models to study how the activation of Erk is coupled to its abundance. Intuitively, Erk activity should rise with increasing amounts of Erk protein. However, a mathematical model shows that the signaling off-state is robust to increasing amounts of Erk, and Erk activity may even decline with increasing amounts of Erk.

https://ift.tt/2wiELQ8