Disease relevance of Prkcz

• In addition to alpha, delta and epsilon-protein kinase C, murine erythroleukemia cells contain zeta-PKC and also a c-PKC isoform, named alpha 1, which shows cross-reactivity with an anti-alpha-PKC antipeptide antibody [1].
• These data suggest that the disregulation of the function of atypical zeta PKC might be involved in the acquisition of an invasive and metastatic phenotype in pancreatic adenocarcinoma cells [2].

High impact information on Prkcz

• Results are shown here demonstrating that the expression of par-4 in NIH-3T3 cells induces morphological changes typical of apoptosis, which are abrogated by cotransfection of either wild-type zeta PKC or lambda/LPKC, but not by their respective kinase-inactive mutants [3].
• Furthermore, by using a dominant kinase-defective mutant of zeta PKC, we confirm that this kinase is required for mitogenic activation in oocytes and fibroblasts [4].
• These results permit us to propose zeta PKC as a critical step downstream of p21ras in mitogenic signal transduction [4].
• Here we have addressed the role that zetaPKC plays in NF-kappaB activation using mice in which this kinase was inactivated by homologous recombination [5].
• Although in zetaPKC-/- EFs this kinase is not necessary for IKK activation, in lung, which abundantly expresses zetaPKC, IKK activation is inhibited [5].

Biological context of Prkcz

• The lack of zetaPKC in embryonic fibroblasts (EFs) severely impairs kappaB-dependent transcriptional activity as well as cytokine-induced phosphorylation of p65 [5].
• Here, we present evidence that the loss of zeta PKC selectively impairs signaling through the B-cell receptor, resulting in inhibition of cell proliferation and survival, as well as defects in the activation of ERK and the transcription of NF-kappa B-dependent genes [6].
• Essential role of RelA Ser311 phosphorylation by zetaPKC in NF-kappaB transcriptional activation [7].
• On the contrary, zeta PKC is not involved in the actin cytoskeleton organization when cells are maintained in IL-4, confirming our previous results showing that IL-4-induced signal transduction is PKC independent [8].
• The signal causes transient, selective down-regulation of mRNA encoding the zeta PKC isoform [9].

Anatomical context of Prkcz

• Role of zeta PKC in B-cell signaling and function [6].
• The lack of zeta PKC produces in mice a number of alterations in the development of secondary lymphoid tissues that could be accounted for, at least in part, by defects in B-cell function [6].
• We report here, using confocal microscopy, that IL-2 induces expression, translocation and association of zeta PKC to a structure coincident with the actin cytoskeleton [8].
• Stimulation of phosphatidylethanolamine (PtdEtn) synthesis by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) has reportedly been found only in hepatocytes expressing the alpha-, betaII-, epsilon-, and zeta-PKC isozymes [10].
• Here we present experimental evidence demonstrating that activation of zeta PKC is not only necessary but also sufficient by itself to activate maturation in oocytes and to produce deregulation of growth control in mouse fibroblasts [4].

Associations of Prkcz with chemical compounds

• These results clearly implicate both Raf-1 and zeta PKC as necessary downstream components for transduction of the mitogenic/oncogenic signal generated by PLC-mediated hydrolysis of phosphatidylcholine and suggest, together with other recent evidence, a bifurcation in the signaling pathway downstream of PC-PLC [11].
• In keeping with this notion, we also demonstrate here that zeta PKC is activated in vitro by ceramide and in vivo by treatment of NIH-3T3 fibroblasts with SMase [12].
• We have used such PC-PLC-transformed cells to evaluate the roles of the cytoplasmic serine/threonine kinases Raf-1, zeta protein kinase C (zeta PKC) and protein kinase A (PKA) in oncogenesis and mitogenic signal transduction elicited by phosphatidylcholine hydrolysis [11].
• Furthermore, results demonstrate that treatment of cells with nocodazole, which disrupts microtubule structures, severely impairs the activity of native zeta PKC, stressing the potential functional relevance of zeta PKC binding to tubulin [13].

Enzymatic interactions of Prkcz

• Here we demonstrate that Ser311 accounts for zetaPKC phosphorylation of RelA and that this site is phosphorylated in vivo in response to TNF-alpha [7].

Regulatory relationships of Prkcz

• These results demonstrate the mechanism whereby zetaPKC regulates NF-kappaB activation in vivo [7].

Other interactions of Prkcz

• The response of Prkcz was found to be similar to that of Prkcd [14].
• We demonstrate here that stable expression of dominant negative mutants of both zeta PKC and Raf-1 lead to reversion of PC-PLC-transformed cells [11].

Analytical, diagnostic and therapeutic context of Prkcz

• We report here the identification by affinity chromatography of tubulin as a zeta PKC-binding protein [13].

References