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Regulatory Role of Diacylglycerol Kinase Gamma in Macrophage Differentiation of Leukemia Cells

Keiko Yamada, Fumio Sakane, Shin ichi Imai, Shuichi Tsushima, Tomohiro Murakami, Hideo Kanoh

Biochem Biophys Res Commun. 2003 May 23;305(1):101-7.

PMID: 12732202

Abstract:

Although nine diacylglycerol kinase (DGK) isozymes have been identified, our knowledge of their individual functions is still limited. Here we report that the levels of DGKgamma mRNA/protein in human leukemia HL-60 and U937 cells were rapidly and markedly decreased upon cellular differentiation into macrophages. In contrast, the enzyme expression remained almost unchanged in granulocytic differentiation pathway. Interestingly, the overexpression of wild-type or constitutively active DGKgamma, but not its kinase-dead mutant, markedly inhibited phorbol ester-induced cell attachment and nonspecific esterase activity, which are hallmarks of macrophage differentiation. We noted in this case that no effects were observed for the corresponding constructs of a closely related isozyme, DGKalpha. Prior to the cell attachment, phorbol ester induced translocation of DGKgamma from the cytoplasm to the cell periphery, resulting in its co-localization with F-actin together with protein kinase Cdelta. The results suggest that DGKgamma negatively regulates macrophage differentiation through its catalytic action operating on the cytoskeleton.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42411920 Protein Kinase Cδ isozyme human Protein Kinase Cδ isozyme human Price
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