The dynamic interplay between adhesion signaling and the ERK MAP kinase pathway
- Author(s): Haling, Jacob Robert
- et al.
Mitogen-activated protein (MAP) kinases and integrins are involved in a variety of processes including but not limited to, cell proliferation, differentiation, survival, and cell migration. Thus it is not surprising that aberrant signaling by either of these elements has developmental and pathological consequences. Whereas, MAP kinases and integrins coordinate these important cellular processes there is a lack of insight into how these two signaling components intersect. In this dissertation I employ a variety of biochemical, molecular biology, and cell biological techniques to decipher three distinct interfaces between integrins and MAP kinases. First, I will demonstrate how PEA-15 potentiates MAP kinase signaling by limiting ERK1/2 association with the plasma membrane. Next I will detail how tyrosine phosphorylation of beta integrin cytoplasmic tails regulates the binding of intracellular binding proteins. Lastly, I will explain how ERK1/2 suppresses integrin activation through the adaptor protein FRS2. In addition, I will provide a biological context for the experimental results discussed in this dissertation