The Journal of Experimental Medicine
ELISpot, FluoroSpot and ELISA kits from Mabtech
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 7 February 2005. doi:10.1084/jem.20031877
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 3, 465-471
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1558K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sebbagh, M.
Right arrow Articles by Bréard, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sebbagh, M.
Right arrow Articles by Bréard, J.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner

Michael Sebbagh1, Jocelyne Hamelin1, Jacques Bertoglio1, Eric Solary2, and Jacqueline Bréard1

1 Institut National de la Santé et de la Recherche Medicale (INSERM) U461, IFR75, Faculté de Pharmacie, 92296 Châtenay-Malabry, France
2 INSERM U517, Faculté de Médecine et de Pharmacie, 21079 Dijon, France

CORRESPONDENCE Jacqueline Bréard: jacqueline.breard{at}cep.u-psud.fr

Caspase activation in target cells is a major function of granzyme B (grB) during cytotoxic lymphocyte granule-induced apoptosis. grB-mediated cell death can occur in the absence of active caspases, and the molecular targets responsible for this additional pathway remain poorly defined. Apoptotic plasma membrane blebbing is caspase independent during granule exocytosis–mediated cell death, whereas in other instances, this event is a consequence of the cleavage by caspases of the Rho effector, Rho-associated coiled coil–containing protein kinase (ROCK) I. We show here that grB directly cleaves ROCK II, a ROCK family member encoded by a separate gene and closely related to ROCK I, and this causes constitutive kinase activity and bleb formation. For the first time, two proteins of the same family are found to be specifically cleaved by either a caspase or grB, thus defining two independent pathways with similar phenotypic consequences in the cells. During granule-induced cell death, ROCK II cleavage by grB would overcome, for this apoptotic feature, the consequences of deficient caspase activation that may occur in virus-infected or malignant target cells.

Abbreviations used: grB, granzyme B; GST, glutathione S-transferase; MLC, myosin regulatory light chain; PS, phosphatidlyserine; ROCK, Rho- associated coiled coil–containing protein kinase; z-VAD-fmk, z-Val-Ala-Asp(Ome)- fluoromethylketone.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS