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

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 C (PKC). PKC 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 PKC were detectable in bone marrow pro-B cells, transition to the pre-B-cell stage was associated with increased relative levels of truncated PKC. We found that PKC 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 PKC 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 PKC results in cell cycle arrest at the G 1 /S transition. These results suggest that the expression and proteolytic activation of PKC play an important role in the regulation of cell division and cell death during early B-cell development.

BASH-novel PKC-Raf-1 pathway of pre-BCR signaling induces κ gene rearrangement

“…PKC, a member of the nPKC subfamily, is expressed in pro-B cells but down-regulated in small pre-B cells, and its overexpression in a pro-B-cell line resulted in cell-cycle arrest. 41 This suggests the involvement of PKC in the transition from pro-B cells to small pre-B cells. PKC mRNA was expressed in BKO84, DKO35, and 18-81 but not in a B-cell line WEHI231 ( Figure 4B).…”

Suppressive Effect of Maslinic Acid on PMA-induced Protein Kinase C in Human B-Lymphoblastoid Cells

“…The PKC family consists of at least 12 serine-threonine kinases which are classified into three major groups: classical (α, β and γ), novel (δ, ε, η, and θ) and atypical (μ, ζ, and ι). According to Brick-Ghannam et al (1994) and Morrow et al (1999), B cells express the cPKC isoforms of α, βI and βII, nPKC isoforms of δ, ε and η, and aPKC of isoform ζ. Thus, seven PKC antibodies were used to determine the types of PKC isoforms expressed in Raji cells.…”

Kinases: positive and negative regulators of apoptosis

“…[274][275][276] Cleavage of these isoforms of PKC results in a catalytic-active fragment which when over-expressed in hematopoietic cells will induce apoptosis. [274][275][276] This mechanism may represent a positive feedback loop that ensures that once the apoptotic process is initiated it goes to completion. Thus, depending on the isoform of PKC activated this family of serine/threonine kinases can have a positive or negative effect on cell survival.…”