Back to Search
Start Over
Alterations in protein kinase C activity and processing during zinc-deficiency-induced cell death.
- Source :
-
The Biochemical journal [Biochem J] 2004 Oct 01; Vol. 383 (Pt 1), pp. 63-71. - Publication Year :
- 2004
-
Abstract
- Protein kinases C (PKCs) are a family of serine/threonine kinases that are critical for signal transduction pathways involved in growth, differentiation and cell death. All PKC isoforms have four conserved domains, C1-C4. The C1 domain contains cysteine-rich finger-like motifs, which bind two zinc atoms. The zinc-finger motifs modulate diacylglycerol binding; thus, intracellular zinc concentrations could influence the activity and localization of PKC family members. 3T3 cells were cultured in zinc-deficient or zinc-supplemented medium for up to 32 h. Cells cultured in zinc-deficient medium had decreased zinc content, lowered cytosolic classical PKC activity, increased caspase-3 processing and activity, and reduced cell number. Zinc-deficient cytosols had decreased activity and expression levels of PKC-alpha, whereas PKC-alpha phosphorylation was not altered. Inhibition of PKC-alpha with Gö6976 had no effect on cell number in the zinc-deficient group. Proteolysis of the novel PKC family member, PKC-delta, to its 40-kDa catalytic fragment occurred in cells cultured in the zinc-deficient medium. Occurrence of the PKC-delta fragment in mitochondria was co-incident with caspase-3 activation. Addition of the PKC-delta inhibitor, rottlerin, or zinc to deficient medium reduced or eliminated proteolysis of PKC-delta, activated caspase-3 and restored cell number. Inhibition of caspase-3 processing by Z-DQMD-FMK (Z-Asp-Gln-Met-Asp-fluoromethylketone) did not restore cell number in the zinc-deficient group, but resulted in processing of full-length PKC-delta to a 56-kDa fragment. These results support the concept that intracellular zinc concentrations influence PKC activity and processing, and that zinc-deficiency-induced apoptosis occurs in part through PKC-dependent pathways.
- Subjects :
- 3T3 Cells
Animals
Caspase 3
Caspases metabolism
Cytosol enzymology
Enzyme Activation
Isoenzymes metabolism
Mice
Protein Kinase C-alpha
Protein Kinase C-delta
Protein Processing, Post-Translational
Subcellular Fractions enzymology
Apoptosis physiology
Protein Kinase C metabolism
Zinc deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1470-8728
- Volume :
- 383
- Issue :
- Pt 1
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 15198639
- Full Text :
- https://doi.org/10.1042/BJ20040074