| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of 1 Pediatrics and 2 Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0656
Ceramide mediates sustained contraction of smooth muscle cells. C2 ceramide induced a rapid increase in Src kinase activity within 15 s, peaked at 1 min, and was sustained up to 8 min. Contraction and Src kinase activity were inhibited in cells incubated in Ca2+-free medium containing 2 mM EGTA and in cells preincubated with herbimycin A, a Src kinase inhibitor. Immunoblotting using a phosphospecific anti-Src (416Y) antibody showed a ceramide-induced increase in pp60src tyrosine phosphorylation. Immunoprecipitation using an anti-phosphotyrosine antibody followed by Western immunoblotting using a monoclonal IgG anti-phosphoinositide 3-kinase NH2 terminal-SH2 domain antibody showed a ceramide-induced increase in phosphoinositide 3-kinase (PI 3-kinase) tyrosine phosphorylation at a protein mass corresponding to 85 kDa, the regulatory subunit of PI 3-kinase, which contains the Src kinase binding site. PI 3-kinase phosphorylation was inhibited by herbimycin A and by the PI 3-kinase inhibitors wortmannin and LY-294002. Preincubation of cells with herbimycin A or PI 3-kinase inhibitors also resulted in an inhibition of mitogen-activated protein (MAP) kinase p42 and p44 activities as seen on Western blots. In summary, we found that 1) the maintenance of sustained contraction is dependent on extracellular Ca2+; 2) ceramide activates a nonreceptor tyrosine kinase pathway through activation of pp60src and PI 3-kinase; and 3) the converging signals are probably through activation of MAP kinase.
rabbit colon; sphingolipids; signal transduction; phosphoinositide 3-kinase
This article has been cited by other articles:
|
|
 |
|
  S. B. Patil and K. N. Bitar RhoA- and PKC-{alpha}-mediated phosphorylation of MYPT and its association with HSP27 in colonic smooth muscle cells. Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G83 - G95. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Czarny and J. E. Schnitzer Neutral sphingomyelinase inhibitor scyphostatin prevents and ceramide mimics mechanotransduction in vascular endothelium Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1344 - H1352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Barsacchi, C. Perrotta, S. Bulotta, S. Moncada, N. Borgese, and E. Clementi Activation of Endothelial Nitric-Oxide Synthase by Tumor Necrosis Factor-alpha : A Novel Pathway Involving Sequential Activation of Neutral Sphingomyelinase, Phosphatidylinositol-3' kinase, and Akt Mol. Pharmacol., April 1, 2003; 63(4): 886 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Y. Shin, Y. P. Lee, T. S. Lee, H. D. Je, D. S. Kim, and U. D. Sohn The Signal Transduction of Endothelin-1-Induced Circular Smooth Muscle Cell Contraction in Cat Esophagus J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 924 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Singer, S. Vang, and W. T. Gerthoffer Coupling of M2 muscarinic receptors to Src activation in cultured canine colonic smooth muscle cells Am J Physiol Gastrointest Liver Physiol, January 1, 2002; 282(1): G61 - G68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Levade, N. Auge, R. J. Veldman, O. Cuvillier, A. Negre-Salvayre, and R. Salvayre Sphingolipid Mediators in Cardiovascular Cell Biology and Pathology Circ. Res., November 23, 2001; 89(11): 957 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Monick, R. K. Mallampalli, A. B. Carter, D. M. Flaherty, D. McCoy, P. K. Robeff, M. W. Peterson, and G. W. Hunninghake Ceramide Regulates Lipopolysaccharide-Induced Phosphatidylinositol 3-Kinase and Akt Activity in Human Alveolar Macrophages J. Immunol., November 15, 2001; 167(10): 5977 - 5985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Limatola, A. M. Mileo, A. Giovannelli, F. Vacca, M. T. Ciotti, D. Mercanti, A. Santoni, and F. Eusebi The Growth-related Gene Product beta Induces Sphingomyelin Hydrolysis and Activation of c-Jun N-terminal Kinase in Rat Cerebellar Granule Neurones J. Biol. Chem., December 17, 1999; 274(51): 36537 - 36543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. I. Ibitayo, J. Sladick, S. Tuteja, O. Louis-Jacques, H. Yamada, G. Groblewski, M. Welsh, and K. N. Bitar HSP27 in signal transduction and association with contractile proteins in smooth muscle cells Am J Physiol Gastrointest Liver Physiol, August 1, 1999; 277(2): G445 - G454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Su, P. Wang, A. Ibitayo, and K. N. Bitar Differential activation of phosphoinositide 3-kinase by endothelin and ceramide in colonic smooth muscle cells Am J Physiol Gastrointest Liver Physiol, April 1, 1999; 276(4): G853 - G861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Wang and K. N. Bitar Rho A regulates sustained smooth muscle contraction through cytoskeletal reorganization of HSP27 Am J Physiol Gastrointest Liver Physiol, December 1, 1998; 275(6): G1454 - G1462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Lee, Y. A. Hannun, and L. M. Obeid Functional Dichotomy of Protein Kinase C (PKC) in Tumor Necrosis Factor-alpha (TNF-alpha ) Signal Transduction in L929 Cells. TRANSLOCATION AND INACTIVATION OF PKC BY TNF-alpha J. Biol. Chem., September 15, 2000; 275(38): 29290 - 29298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Versteeg, I. Hoedemaeker, S. H. Diks, J. C. Stam, M. Spaargaren, P. M. P. van Bergen en Henegouwen, S. J. H. van Deventer, and M. P. Peppelenbosch Factor VIIa/Tissue Factor-induced Signaling via Activation of Src-like Kinases, Phosphatidylinositol 3-Kinase, and Rac J. Biol. Chem., September 8, 2000; 275(37): 28750 - 28756. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
