Rapid Changes in the Phosphoproteome Show Diverse Cellular Responses Following Stimulation of Human Lung Fibroblasts with Endothelin-1

The rapid phosphorylation and dephosphorylation of a variety of proteins downstream of the endothelin receptors A and B was investigated following stimulation of human lung fibroblasts with endothelin-1. Changes in the phosphorylation of proteins involved in the cell cycle, cytoskeleton, membrane channels, transcription, angiogenesis, and metabolism were observed. From observed changes in protein phosphatase 2A, CDC25 A, and caspase-2 precursor, a model for the promotion of cell cycle progression by ET-1 stimulation is proposed. This may offer insights into the mechanisms by which ET-1 exerts its mitogenic effects. The identities of the other proteins phosphorylated within 2 min of stimulation indicate that endothelin-1 also rapidly engages a diverse variety of other cellular responses.