PRKCD Gene

The PRKCD gene (PRKCD-is the acronym for "protein kinase C delta") is a protein-coding gene located on chromosome 3p21.1. The protein encoded by the PRKCD gene is a member of the protein kinase C family of serine- and threonine-specific protein kinases. The encoded protein is activated by diacylglycerol and is both a tumor suppressor and a positive regulator of cell cycle progression. In addition, this protein kinase can positively or negatively regulate apoptosis.

Furthermore, the kinase negatively affects B cell proliferation and also has an important function in the induction of B cell tolerance by self-antigen. It activates the promoter of the apoptosis-bringing transcription factor BCLAF1/Btf upon DNA damage to induce gene transcription and apoptosis. Upon ER stress or DNA damage-triggered apoptosis, it can form a complex with the tyrosine protein kinase ABL1 that triggers apoptosis independently of p53/TP53(Duquesnes N et al. 2011).

In the cytosol, protein kinase C Delta can induce apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1, and decreasing the level of X-linked inhibitor of apoptosis protein(XIAP), whereas in the nucleus it induces apoptosis via activation of MAPK8 or MAPK9.

Following ionizing radiation treatment , the kinase is required for activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial apoptosis pathway. Can phosphorylate and degrade MCL1, which is sufficient to trigger BAX activation and apoptosis.

Protein kinase C Delta is required for cell cycle progression control in both G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression in G1/S phase by upregulating CDK inhibitor CDKN1A/p21 and inhibiting CCNA2 promoter activity. In response to UV irradiation, it can phosphorylate CDK1, which is important for activation of the G2/M-DNA damage checkpoint. The kinase can protect glioma cells from TNFSF10/TRAIL-induced apoptosis, probably by inducing increased phosphorylation and subsequent activation of AKT1.

Protein kinase C Delta is highly expressed in a number of cancer cells and promotes cell survival and resistance to chemotherapeutic agents by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1. This occurs through several signaling pathways that promote survival, including NF-kappaB, AKT1, and MAPK1/3(ERK1/2).

The kinase is involved in antifungal immunity by mediating phosphorylation and activation of CARD9 following activation of C-type lectin receptors and promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways . May also act as a tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, it is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity and regulates TNF-triggered superoxide anion production in neutrophils through direct phosphorylation and activation of NCF1 or indirectly via MAP kinases1/3 (ERK1/2) signaling pathways (Zeidan YH et al 2007).

Diseases associated with PRKCD include autoimmune lymphoproliferative syndrome, type III.

1. Andre JM et al (2007) Overexpression of the antiapoptotic gene Bfl-1 in B cells from patients with familial systemic lupus erythematosus. Lupus 16: 95-100.
2. Belot A et al. (2013) Protein kinase C-delta deficiency causes mendelian systemic lupus erythematosus with B cell-defective apoptosis and hyperproliferation. Arthritis Rheum 65: 2161-2171.
3. Duquesnes N et al. (2011) PKC-delta and PKC-epsilon: foes of the same family or strangers? J Mol Cell Cardiol 51:665-673)
4. (Zeidan YH et al. (2007) Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation. J Biol Chem 282:11549-1161).