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Molecular and Cellular Biology, August 1999, p. 5608-5618, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Pro-B-Cell-Specific Transcription and Proapoptotic Function of Protein Kinase Ceta

Theresa A. Morrow,1 Stefan A. Muljo,1 Jun Zhang,2 J. Marie Hardwick,2 and Mark S. Schlissel1,*

Graduate Program in Immunology1 and Department of Molecular Microbiology & Immunology,2 The Johns Hopkins University School of Public Health, Baltimore, Maryland 21205

Received 11 December 1998/Returned for modification 2 February 1999/Accepted 20 May 1999

Using a subtractive cloning scheme on cDNA prepared from primary pro-B and pre-B cells, we identified several genes whose products regulate apoptosis. We further characterized one of these genes, encoding protein kinase Ceta (PKCeta ). PKCeta transcripts were readily detected in pro-B cells but were absent in pre-B cells. Although both a full-length and a truncated form of PKCeta were detectable in bone marrow pro-B cells, transition to the pre-B-cell stage was associated with increased relative levels of truncated PKCeta . We found that PKCeta is proteolyzed in apoptotic lymphocytes, generating a kinase-active fragment identical to the truncated form which is capable of inducing apoptosis when expressed in a pro-B cell line. Caspase-3 can generate an identical PKCeta cleavage product in vitro, and caspase inhibitors prevent the generation of this product during apoptosis in transfected cell lines. Inducible overexpression of either the full-length or truncated form of PKCeta results in cell cycle arrest at the G1/S transition. These results suggest that the expression and proteolytic activation of PKCeta play an important role in the regulation of cell division and cell death during early B-cell development.


* Corresponding author. Present address: Department of Molecular and Cell Biology, LSA 439, University of California, Berkeley, CA 94720. Phone: (510) 643-2462. E-mail: mss{at}uclink4.berkeley.edu.edu.


Molecular and Cellular Biology, August 1999, p. 5608-5618, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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