@article {185,
	title = {Creatine kinase, an ATP-generating enzyme, is required for thrombin receptor signaling to the cytoskeleton.},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {97},
	year = {2000},
	month = {2000 Oct 24},
	pages = {12062-7},
	abstract = {<p>Thrombin orchestrates cellular events after injury to the vascular system and extravasation of blood into surrounding tissues. The pathophysiological response to thrombin is mediated by protease-activated receptor-1 (PAR-1), a seven-transmembrane G protein-coupled receptor expressed in the nervous system that is identical to the thrombin receptor in platelets, fibroblasts, and endothelial cells. Once activated by thrombin, PAR-1 induces rapid and dramatic changes in cell morphology, notably the retraction of growth cones, axons, and dendrites in neurons and processes in astrocytes. The signal is conveyed by a series of localized ATP-dependent reactions directed to the actin cytoskeleton. How cells meet the dynamic and localized energy demands during signal transmission is unknown. Using the yeast two-hybrid system, we identified an interaction between PAR-1 cytoplasmic tail and the brain isoform of creatine kinase, a key ATP-generating enzyme that regulates ATP within subcellular compartments. The interaction was confirmed in vitro and in vivo. Reducing creatine kinase levels or its ATP-generating potential inhibited PAR-1-mediated cellular shape changes as well as a PAR-1 signaling pathway involving the activation of RhoA, a small G protein that relays signals to the cytoskeleton. Thrombin-stimulated intracellular calcium release was not affected. Our results suggest that creatine kinase is bound to PAR-1 where it may be poised to provide bursts of site-specific high-energy phosphate necessary for efficient receptor signal transduction during cytoskeletal reorganization.</p>
},
	keywords = {Adenosine Triphosphate, Animals, Base Sequence, Calcium, Creatine Kinase, Cytoskeleton, Oligonucleotides, Antisense, Rats, Receptor, PAR-1, Receptors, Thrombin, Signal Transduction, Two-Hybrid System Techniques},
	author = {Mahajan, V B and Pai, K S and Lau, A and Cunningham, D D}
}
