title: The structure and functions of human lysophosphatidic acid acyltransferases.
abstract: Lysophosphatidic acid (LPA) and phosphatidic acid (PA) are two phospholipids involved in signal transduction and in lipid biosynthesis in cells. LPA acyltransferase (LPAAT), also known as 1-acyl sn-glycerol-3-phosphate acyltransferase (1-AGPAT) (EC 2.3.1.51), catalyzes the conversion of LPA to PA. Two human isoforms of LPAAT, designated as LPAAT-alpha (AGPAT1) and LPAAT-beta (AGPAT2), have been extensively characterized. These two proteins contain extensive sequence similarities to microbial, plant and animal LPAAT sequences. LPAAT-alpha mRNA is uniformly expressed throughout most tissues with the highest level found in skeletal muscle; whereas LPAAT-beta is differentially expressed, with the highest level found in heart and liver, and negligible level in brain and placenta. The LPAAT-alpha gene is located on chromosome 6p21.3, an area within the class III region of the major hiscompatibility complex (MHC) and the LPAAT-beta gene is mapped to chromosome 9q34.3. Enhanced transcription of LPAAT-beta is suggested for neoplasm of the female genital tract. Additionally, ectopic LPAAT expression in certain cytokine-responsive cell lines can effect amplification of cellular signaling processes, such as those leading to enhancement of synthesis of tumor necrosis factor-alpha and interleukin-6 from cells following stimulation with interleukin-1beta; this suggests that the LPAAT genes represent candidates for affecting the development of certain cancers or inflammation-associated diseases.
authors.affiliation: Cell Therapeutics, Inc., Seattle, WA 98119, USA. dleung@ctiseattle.com
authors.forename: D W
authors.initials: DW
authors.lastname: Leung
mesh_terms: D000217:Acyltransferases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D016207:Cytokines / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics; D006649:Histocompatibility Antigens / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D018411:Spodoptera / Q000235:genetics; D014018:Tissue Distribution
chemical_list: D016207:Cytokines; D006649:Histocompatibility Antigens; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase