DEVELOPMENTALLY EXPRESSED MYOSIN HEAVY-CHAIN KINASE POSSESSES A DIACYLGLYCEROL KINASE DOMAIN

In Dictyostelium, an ordered actin and myosin assembly-disassembly pro cess is necessary for proper development, differentiation, and motilit y (Yumura S, Fukui F, 1985, Nature 314(6007):194-196; Ravid S, Spudich JA, 1989, J Biol Chem 264(25):15144-15150), and phosphorylation of my osin heavy chains has been implicated in the myosin assembly-disassemb ly process (Egelhoff TT, Lee RJ, Spudich JA, 1993, Cell 75(2):363-371) . The developmentally expressed 84-kDa myosin heavy chain kinase (MHCK ) from Dictyostelium (Ravid S, Spudich JA, 1992, Proc Natl Acad Sci US A 89(13):5877-5881) is known to be a member of the protein kinase C (P KC) family. We have observed a rather striking homology between the la rge central domain of MHCK and the catalytic domain of diacylglycerol kinase (DGK), indicating that MHCK is in fact a gene fusion between a DGK and a PKC, possessing two separate kinase domains. The combined di acylglycerol kinase/myosin heavy-chain kinase (DGK/MHCK) may therefore have dual Functionality, possessing the ability to phosphorylate both protein and lipid. We present a hypothesis that DGK/MHCK can antagoni ze both actin and myosin assembly, as well as other cellular processes , by coordinated down regulation of signaling via myosin heavy-chain k inase activity and diacylglycerol kinase activity.