Pro-B-cell-specific transcription and proapoptotic function of protein kinase Cη

Theresa A. Morrow, Stefan A. Muljo, Jun Zhang, J. Marie Hardwick, Mark S. Schlissel

Research output: Contribution to journalArticlepeer-review

Abstract

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 Cη (PKCη). PKCη 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 PKCη were detectable in bone marrow pro-B cells, transition to the pre-B-cell stage was associated with increased relative levels of truncated PKCη. We found that PKCη 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 PKCη 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 PKCη results in cell cycle arrest at the G1/S transition. These results suggest that the expression and proteolytic activation of PKCη play an important role in the regulation of cell division and cell death during early B-cell development.

Original languageEnglish (US)
Pages (from-to)5608-5618
Number of pages11
JournalMolecular and cellular biology
Volume19
Issue number8
DOIs
StatePublished - Aug 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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