HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print May 3, 2005

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0205070v1 78/2/503    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mourtada-Maarabouni, M. Articles by Williams, G. T. Search for Related Content PubMed PubMed Citation Articles by Mourtada-Maarabouni, M. Articles by Williams, G. T.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0205070

Received for publication February 4, 2005.
Revised March 18, 2005.
Accepted for publication April 1, 2005.

Article

Functional expression cloning reveals a central role for the receptor for activated protein kinase C 1 (RACK1) in T cell apoptosis

Mirna Mourtada-Maarabouni ^*@, Lucy Kirkham ^*, Farzin Farzaneh , and Gwyn T. Williams ^*@

*School of Life Sciences, Keele University, United Kingdom; and Department of Haematological and Molecular Medicine, Rayne Institute, GKT School of Medicine, London, United Kingdom

^@ To whom correspondence should be addressed. E-mail: g.t.williams{at}keele.ac.uk.

	Abstract

Mammalian cDNA expression cloning was used to identify novel genes that regulate apoptosis. Using a functional screen, we identified a partial cDNA for the receptor for activated protein kinase C 1 (RACK1) through selection for resistance to phytohemagglutinin and -irradiation. Expression of this partial cDNA in T cell lines using a mammalian expression vector produced an increase in RACK1 expression and resulted in resistance to dexamethasone- and ultraviolet-induced apoptosis. Down-regulation of RACK1 using RNA interference abolished the resistance of the transfected cells to apoptosis. Overexpression of full-length RACK1 also resulted in the suppression of apoptosis mediated by several apoptotic stimuli, and this effect was quantitatively consistent with the effects of the original cDNA isolated on endogenous RACK1 levels. Together, these findings suggest that RACK1 plays an important role in the intracellular signaling pathways that lead to apoptosis in T cells.

Key Words: WD-40 • cell death • forward genetics

This article has been cited by other articles:

				W. Zhang, G. Z. Cheng, J. Gong, U. Hermanto, C. S. Zong, J. Chan, J. Q. Cheng, and L.-H. Wang RACK1 and CIS Mediate the Degradation of BimEL in Cancer Cells J. Biol. Chem., June 13, 2008; 283(24): 16416 - 16426. [Abstract] [Full Text] [PDF]