Distinct 1-monoacylglycerol and 2-monoacylglycerol kinase activities of diacylglycerol kinase isozymes

• Type I–III DGKs (α, β, γ, δ, η, κ and ε) have relatively stronger 2-MGK activity than 1-MGK activity.
• Type IV DGKs (ζ and ι) only have negligible 1-MGK and 2-MGK activities.
• Type V DGK (θ) has stronger 1-MGK activity than 2-MGK activity.
• These differences may affect the pathophysiological functions of each DGK isozyme.

Diacylglycerol kinase (DGK) consists of ten isozymes and is involved in a wide variety of patho-physiological events. However, the enzymological properties of DGKs have not been fully understood. In this study, we performed a comprehensive analysis on the 1-monoacylglycerol kinase (MGK) and 2-MGK activities of ten DGK isozymes. We revealed that type I (α, β and γ), type II (δ, η and κ) and type III (ε) DGKs have 7.9–19.2% 2-MGK activity compared to their DGK activities, whereas their 1-MGK activities were < 3.0%. Both the 1-MGK and 2-MGK activities of the type IV DGKs (ζ and ι) were < 1% relative to their DGK activities. Intriguingly, type V DGKθ has approximately 6% 1-MGK activity and < 2% 2-MGK activity compared to its DGK activity. Purified DGKθ exhibited the same results, indicating that its 1-MGK activity is intrinsic. Therefore, DGK isozymes are categorized into three types with respect to their 1-MGK and 2-MGK activities: those having (1) 2-MGK activity relatively stronger than their 1-MGK activity (types I–III), (2) only negligible 1-MGK and 2-MGK activities (type IV), and (3) 1-MGK activity stronger than its 2-MGK activity (type V). The 1-MGK activity of DGKθ and the 2-MGK activity of DGKα were stronger than those of the acylglycerol kinase reported as 1-MGK and 2-MGK to date. The presence or absence of 1-MGK and 2-MGK activities may be essential to the patho-physiological functions of each DGK isozyme.

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