Published online before print October 24, 2002, doi: 10.1161/01.RES.0000042702.04920.BF
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 25, 2002
Revised on October 10, 2002
Accepted on October 10, 2002
Involvement of Src Family Protein Tyrosine Kinases in Ca2+ Sensitization of Coronary Artery Contraction Mediated by a Sphingosylphosphorylcholine-Rho-Kinase Pathway
Fumiaki Nakao ;
From the Departments of Cardiovascular Medicine (F.N., M.M.) and Molecular Physiology (F.N., S.K., K.M., Y.M., S.S., S.M., N.T.-I.), Yamaguchi University School of Medicine, Yamaguchi, Japan; and the First Department of Internal Medicine (M.I.), Mie University School of Medicine, Mie, Japan.
* To whom correspondence should be addressed. E-mail: seikoba{at}yamaguchi-u.ac.jp.
We recently reported that sphingosylphosphorylcholine (SPC) is a novel messenger for Rho-kinase-mediated Ca2+ sensitization of vascular smooth muscle (VSM) contraction. Subcellular localization and kinase activity of Src family protein kinases (SrcPTKs), except for c-Src, is controlled by a reversible S-palmitoylation, an event inhibited by eicosapentaenoic acid (EPA). We examined the possible involvement of SrcPTKs in SPC-induced Ca2+ sensitization and effects of EPA. We used porcine coronary VSM and rat aortic VSM cells (VSMCs) in primary culture. An SrcPTKs inhibitor, PP1, and EPA inhibited SPC-induced contraction, concentration-dependently, without affecting [Ca2+]i levels and the Ca2+-dependent contraction induced by high K+ depolarization. A digitized immunocytochemical analysis in VSMCs revealed that SPC induced translocation of Fyn, but not of c-Src, from the cytosol to the cell membrane, an event abolished by EPA. Translocation of Rho-kinase from the cytosol to the cell membrane by SPC was also inhibited by EPA and PP1. The SPC-induced activation of SrcPTKs was blocked by EPA and PP1, but not by Y27632, an Rho-kinase inhibitor. Rho-kinase-dependent phosphorylation of myosin phosphatase induced by SPC was inhibited by EPA, PP1, and Y27632. Translocation and activation of SrcPTKs, including Fyn, play an important role in Ca2+ sensitization of VSM contractions mediated by a SPC-Rho-kinase pathway.
Key words: sphingosylphosphorylcholine • Ca2+ sensitization • Src family protein tyrosine kinase • eicosapentaenoic acid • S-palmitoylation
This article has been cited by other articles:
 |
|
 |
|
  G. A. Knock, V. A. Snetkov, Y. Shaifta, S. Drndarski, J. P.T. Ward, and P. I. Aaronson Role of src-family kinases in hypoxic vasoconstriction of rat pulmonary artery Cardiovasc Res, August 23, 2008; (2008) cvn209v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lu, A. Alioua, Y. Kumar, P. Kundu, M. Eghbali, N. V. Weisstaub, J. A. Gingrich, E. Stefani, and L. Toro c-Src tyrosine kinase, a critical component for 5-HT2A receptor-mediated contraction in rat aorta J. Physiol., August 15, 2008; 586(16): 3855 - 3869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Knock, Y. Shaifta, V. A. Snetkov, B. Vowles, S. Drndarski, J. P.T. Ward, and P. I. Aaronson Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery Cardiovasc Res, February 1, 2008; 77(3): 570 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Snetkov, G. D. Thomas, B. Teague, R. M. Leach, Y. Shaifta, G. A. Knock, P. I. Aaronson, and J. P.T. Ward Low Concentrations of Sphingosylphosphorylcholine Enhance Pulmonary Artery Vasoreactivity: The Role of Protein Kinase C{delta} and Ca2+ Entry Hypertension, February 1, 2008; 51(2): 239 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kinoshita, N. Matsuda, Y. Kimoto, S. Tohyama, K. Hama, K. Nakahata, and Y. Hatano Sevoflurane, but Not Propofol, Prevents Rho Kinase-Dependent Contraction Induced by Sphingosylphosphorylcholine in the Porcine Coronary Artery Anesth. Analg., August 1, 2007; 105(2): 325 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Wardle, M. Gu, Y. Ishida, and R. J. Paul Rho kinase is an effector underlying Ca2+-desensitizing hypoxic relaxation in porcine coronary artery Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H23 - H29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Li, H. Tanaka, H. H. Wang, S. Yoshiyama, H. Kumagai, A. Nakamura, D. L. Brown, S. E. Thatcher, G. L. Wright, and K. Kohama Intracellular signal transduction for migration and actin remodeling in vascular smooth muscle cells after sphingosylphosphorylcholine stimulation Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1262 - H1272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Morikage, H. Kishi, M. Sato, F. Guo, S. Shirao, T. Yano, M. Soma, K. Hamano, K. Esato, and S. Kobayashi Cholesterol Primes Vascular Smooth Muscle to Induce Ca2 Sensitization Mediated by a Sphingosylphosphorylcholine-Rho-Kinase Pathway: Possible Role for Membrane Raft Circ. Res., August 4, 2006; 99(3): 299 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Pertel, D. Zhu, R. A. Panettieri, N. Yamaguchi, C. W. Emala, and C. A. Hirshman Expression and muscarinic receptor coupling of Lyn kinase in cultured human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L492 - L500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Weigand, J. T. Sylvester, and L. A. Shimoda Mechanisms of endothelin-1-induced contraction in pulmonary arteries from chronically hypoxic rats Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L284 - L290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Thomas, V. A. Snetkov, R. Patel, R. M. Leach, P. I. Aaronson, and J. P.T. Ward Sphingosylphosphorylcholine-induced vasoconstriction of pulmonary artery: Activation of non-store-operated Ca2+ entry Cardiovasc Res, October 1, 2005; 68(1): 56 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Che and P. K. Carmines Src family kinase involvement in rat preglomerular microvascular contractile and [Ca2+]i responses to ANG II Am J Physiol Renal Physiol, April 1, 2005; 288(4): F658 - F664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Jernigan, B. R. Walker, and T. C. Resta Chronic hypoxia augments protein kinase G-mediated Ca2+ desensitization in pulmonary vascular smooth muscle through inhibition of RhoA/Rho kinase signaling Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1220 - L1229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cherukuri, R. H. Carter, S. Brooks, W. Bornmann, R. Finn, C. S. Dowd, and S. K. Pierce B Cell Signaling Is Regulated by Induced Palmitoylation of CD81 J. Biol. Chem., July 23, 2004; 279(30): 31973 - 31982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. SOMLYO and A. V. SOMLYO Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase Physiol Rev, October 1, 2003; 83(4): 1325 - 1358. [Abstract] [Full Text] [PDF]
|
|