The structure and functions of human lysophosphatidic acid acyltransferases

Lysophosphatidic acid (LPA) and phosphatidic acid (PA) are two phospholipid s involved in signal transduction and in lipid biosynthesis in cells. LPA a cyltransferase (LPAAT), also known as 1-acyl sn-glycerol-3-phosphate acyltr ansferase (1-AGPAT) (EC 2.3.1.51), catalyzes the conversion of LPA to PA. T wo human isoforms of LPAAT, designated as LPAAT-alpha (AGPAT1) and LPAAT-be ta (AGPAT2), have been extensively characterized. These two proteins contai n extensive sequence similarities to microbial, plant and animal LPAAT sequ ences. LPAAT-alpha mRNA is uniformly expressed throughout most tissues with the highest level found in skeletal muscle; whereas LPAAT-beta is differen tially expressed, with the highest level found in heart and liver, and negl igible level in brain and placenta. The LPAAT-alpha gene is located on chro mosome 6p21.3, an area within the class III region of the major hiscompatib ility complex (MHC) and the LPAAT-beta gene is mapped to chromosome 9q34.3. Enhanced transcription of LPAAT-beta is suggested for neoplasm of the fema le genital tract. Additionally, ectopic LPAAT expression in certain cytokin e-responsive cell lines can effect amplification of cellular signaling proc esses, such as those leading to enhancement of synthesis of tumor necrosis factor-alpha and interleukin-6 from cells following stimulation with interl eukin-1 beta; this suggests that the LPAAT genes represent candidates for a ffecting the development of certain cancers or inflammation-associated dise ases.