Disease relevance of Dgkz

• Furthermore, DGKzeta-deficient mice mounted a more robust immune response to lymphocytic choriomeningitis virus infection than did wild-type mice [1].

High impact information on Dgkz

• When stimulated in anergy-producing conditions, T cells lacking DGK-alpha or DGK-zeta proliferated and produced interleukin 2 [2].
• Previous studies have shown that diacylglycerol kinase zeta (DGKzeta), which converts diacylglycerol to phosphatidic acid, can inhibit TCR signaling [1].
• Impaired degranulation but enhanced cytokine production after Fc epsilonRI stimulation of diacylglycerol kinase zeta-deficient mast cells [3].
• Moreover, DGK-zeta directly interacts with Rac1 through a binding site located within its C1 domains [4].
• This effect was independent of DGK-zeta kinase activity but dependent on a functional C-terminal PDZ-binding motif, which specifically interacts with syntrophin PDZ domains [4].

Biological context of Dgkz

• Syntrophins are scaffold proteins that regulate the subcellular localization of diacylglycerol kinase zeta (DGK-zeta), an enzyme that phosphorylates the lipid second-messenger diacylglycerol to yield phosphatidic acid [4].
• Binding of DGKzeta to pRB is dependent on the phosphorylation status of pRB, since only hypophosphorylated pRB interacts with DGKzeta [5].
• Finally, overexpression of DGKzeta in pRB-null fibroblasts reconstitutes a cell cycle arrest induced by gamma-irradiation [5].
• Moreover, DGK-zeta co-localized and interacted with phosphoinositide-specific phospholipase Cbeta1 (PLCbeta1), that is involved in inositide-dependent signaling pathways important for the regulation of cell proliferation and differentiation [6].
• Furthermore, we report that DGK-zeta associated with nuclear matrix, the fundamental organizing principle of the nucleus where many cell functions take place, including DNA replication, gene expression, and protein phosphorylation [6].

Anatomical context of Dgkz

• Regulation of neurite outgrowth in N1E-115 cells through PDZ-mediated recruitment of diacylglycerol kinase zeta [4].
• Here we show that DGKzeta-deficient T cells are hyperresponsive to TCR stimulation both ex vivo and in vivo [1].
• Subnuclear localization and differentiation-dependent increased expression of DGK-zeta in C2C12 mouse myoblasts [6].
• Overall, our findings further support the importance of speckles and nuclear matrix in lipid-dependent signaling and suggest that nuclear DGK-zeta might play some fundamental role during myogenic differentiation of C2C12 cells [6].
• In E13.5 embryos, DGKzeta mRNA was highly expressed in vibrissa follicles, in spinal ganglia, and in the interdigital regions of the developing limbs [7].

Regulatory relationships of Dgkz

• Several lines of evidence suggest DGK-zeta promotes neurite outgrowth through association with the GTPase Rac1 [4].

Analytical, diagnostic and therapeutic context of Dgkz

• DGK-zeta was present in the nuclear speckle domains, as also revealed by immuno-electron microscopy analysis [6].
• Immunocytochemistry coupled to confocal laser scanning microscopy showed that both endogenous and green fluorescent protein-tagged overexpressed DGK-zeta localized mostly to the nucleus [6].
• Northern blotting showed that DGKzeta expression was limited to specific anatomical regions of the brain [7].

References