| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | ADVANCED SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
2 Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe 657-8501, Japan
Protein kinase C (PKC) is translocated to various cellular regions in a subtype and stimulation-dependent manner. Thereafter, the activated PKC phosphorylates its substrate and causes subsequent cellular responses (PKC targeting). The 3-phosphoinositide-dependent protein kinase-1 (PDK1) has an essential role in the maturation of PKC by phosphorylating a threonine residue in the PKC activation loop. To elucidate the role of PDK1 in PKC targeting, we expressed mutant 
- or 
-PKC fused with GFP (- or -PKC-ALM (activation loop mutant)-GFP), whose threonine residue in the activation loop was replaced with alanine, and compared their P2Y receptor-mediated translocation with wild-type PKC-GFP in CHO cells. ATP (1 mM) induced the transient translocation of wild-type - or -PKC-GFP from cytoplasm to plasma membrane and following retranslocation from membrane to the cytoplasm. - or -PKC-ALM-GFP was also translocated to plasma membrane, which was, however, retained at the membrane for a longer period than wild type. Similar results were observed in kinase-negative PKC mutants, indicating that the phosphorylation by PDK1 affects the retranslocation step of PKC by regulating the kinase activity. The simultaneous monitoring of [Ca2+]i and diacylglycerol (DG) levels with the translocation of PKC demonstrated that PKC-ALM induced the prolonged accumulation of DG, resulting in the prolonged retention of PKC-ALM at the plasma membrane. It is possible that PKC-ALM with decreased kinase activity could delay the conversion of DG at the plasma membrane. Our present study suggests that the activation loop phosphorylation plays an important role in receptor-mediated PKC targeting.
*Correspondence: E-mail: nsakai{at}hiroshima-u.ac.jp
This article has been cited by other articles:
|
|
 |
|
  T. Ikegami, L. Krilov, J. Meng, B. Patel, K. Chapin-Kennedy, and B. Bouscarel Decreased Glucagon Responsiveness by Bile Acids: A Role for Protein Kinase C{alpha} and Glucagon Receptor Phosphorylation Endocrinology, November 1, 2006; 147(11): 5294 - 5302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Seki, N. Irie, K. Nakamura, H. Sakaue, W. Ogawa, M. Kasuga, H. Yamamoto, S. Ohmori, N. Saito, and N. Sakai Fused protein of deltaPKC activation loop and PDK1-interacting fragment (deltaAL-PIF) functions as a pseudosubstrate and an inhibitory molecule for PDK1 when expressed in cells. Genes Cells, September 1, 2006; 11(9): 1051 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Brizuela, M. Rabano, A. Pena, P. Gangoiti, J. M. Macarulla, M. Trueba, and A. Gomez-Munoz Sphingosine 1-phosphate: a novel stimulator of aldosterone secretion J. Lipid Res., June 1, 2006; 47(6): 1238 - 1249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Collazos, B. Diouf, N. C. Guerineau, C. Quittau-Prevostel, M. Peter, F. Coudane, F. Hollande, and D. Joubert A Spatiotemporally Coordinated Cascade of Protein Kinase C Activation Controls Isoform-Selective Translocation. Mol. Cell. Biol., March 1, 2006; 26(6): 2247 - 2261. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | ADVANCED SEARCH | TABLE OF CONTENTS |
