Activation of tyrosine kinases by reactive oxygen species in vascular smooth muscle cells: significance and involvement of EGF receptor transactivation by angiotensin II.
Enhanced production of reactive oxygen species (ROS) such as H(2)O(2) and a failure in ROS removal by scavenging systems are hallmarks of several cardiovascular diseases such as atherosclerosis and hypertension. ROS act as second messengers that play a prominent role in intracellular signaling and cellular function. In vascular smooth muscle cells (VSMCs), a vascular pathogen, angiotensin II, appears to initiate growth-promoting signal transduction through ROS-sensitive tyrosine kinases. However, the precise mechanisms by which tyrosine kinases are activated by ROS remain unclear. In this review, the current knowledge that suggests how certain tyrosine kinases are activated by ROS, along with their functional significance in VSMCs, will be discussed. Recent findings suggest that transactivation of the epidermal growth factor receptor by ROS requires metalloprotease-dependent heparin-binding epidermal growth factor-like growth factor production, whereas other ROS-sensitive tyrosine kinases such as PYK2, JAK2, and platelet-derived growth factor receptor require activation of protein kinase C-delta. Each of these ROS-sensitive kinases could mediate specific signaling critical for pathophysiological responses. Detailed analysis of the mechanism of cross-talk and the downstream function of these various tyrosine kinases will yield new therapeutic interventions for cardiovascular disease.
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Gerald D
GD
Frank
Satoru
S
Eguchi
D000818:Animals; D002318:Cardiovascular Diseases / Q000473:pathology; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species; D012307:Risk Factors; D015398:Signal Transduction; D015533:Transcriptional Activation
D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases