Cellular signaling by endothelin peptides: pathways to the nucleus.
Endothelins (ET) are potent regulatory peptides that evoke diverse responses in glomerular mesangial cells. These include short-term actions, such as contraction and secretion, and long-term, adaptive responses, such as cell growth. Although much attention has been focused on the second messenger cascades, which govern short-term effects, the pathways of cytosolic and nuclear signaling, which effect long-term changes, remain unclear. Several distal signaling events by ET receptors have been characterized in rat mesangial cells. These include activation of a cytosolic protein kinase, mitogen-activated protein kinase and an inducible transcription factor, activator protein-1 (AP-1). This review focuses on the activation of mitogen-activated protein kinase and activator protein-1 by ET and discusses the potential role of these third and fourth messengers in controlling long-term cellular adaptations. Characterization of these and other cytosolic and nuclear signals should provide important insights into the pleiotropic actions of ET peptides.
Simonson
M S
MS
Department of Medicine, Case Western Reserve University, University Hospitals, Cleveland, OH 44106.
Wang
Y
Y
Dunn
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D016232:Endothelins / Q000235:genetics / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D017466:Receptors, Endothelin
D016232:Endothelins; D021382:Protein Sorting Signals; D016755:Proto-Oncogene Proteins c-jun; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D011494:Protein Kinases; D002118:Calcium