The Importance of Tyrosine Phosphorylation Control of Cellular Signaling Pathways in Respiratory Disease: pY and pY Not.

Abstract

Reversible phosphorylation of proteins on tyrosine residues is an essential signaling mechanism by which diverse cellular processes are closely regulated. The tight temporal and spatial control of the tyrosine phosphorylation status of proteins by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) is critical to cellular homeostasis as well as to adaptations to the external environment. Via regulation of cellular signaling cascades involving other protein kinases and phosphatases, receptors, adaptor proteins, and transcription factors, PTKs and PTPs closely control diverse cellular processes such as proliferation, differentiation, migration, inflammation, and maintenance of cellular barrier function. Given these key regulatory roles, it is not surprising that dysfunction of PTKs and PTPs is important in the pathogenesis of human disease, including many pulmonary diseases. The roles of various PTKs and PTPs in acute lung injury and repair, pulmonary fibrosis, pulmonary vascular disease, and inflammatory airway disease are discussed in this review. It is important to note that although there is overlap among many of these proteins in various disease states, the mechanisms by which they influence the pathogenesis of these conditions differ, suggesting wide-ranging roles for these enzymes and their potential as therapeutic targets.