Cellular Signal Transduction in Toxicology and Pharmacology

4Signal Transduction in Disease: Relating Cell Signaling to Morbidity and Mortality

Patricia E. Ganey¹ and Sean A. Misek²

¹ Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA

² Department of Physiology, Michigan State University, East Lansing, MI, USA

4.1 Introduction

Disease pathogenesis can often arise from disruptions in normal signaling pathways, which are often complex and integrated. For example, perturbations in intracellular calcium homeostasis have been implicated in the development of neurodegenerative diseases such as Parkinson's, Huntington's, and Alzheimer's disease [1–3]. Additionally, simple dysregulation of signal transduction cascades in response to alterations in the local cellular environment (e.g. oxidative stress, endoplasmic reticulum stress, mitogen‐activated protein kinase (MAPK) activity, and alterations in calcineurin, to name a few [1, 4–7]) has also been shown to contribute to disease pathogenesis. Further, perturbations in signal transduction networks can lead to altered physiological states, such as asthma and diabetes. Asthma arises from disruption of inter‐ and intracellular signaling in inflammatory cells, as well as alterations in the molecular machinery for synthesis of mucus; these changes involve lipid mediators, cytokines, T cells, and innate lymphoid cells [8–11]. Disruption of pathways signaling through Notch, MAPKs, phosphoinositide‐3‐kinase (PI3K), and protein tyrosine kinases (PTKs) has been shown to ...