The structure and functions of human lysophosphatidic acid acyltransferases.
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.
Leung
D W
DW
Cell Therapeutics, Inc., Seattle, WA 98119, USA. dleung@ctiseattle.com
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
D016207:Cytokines; D006649:Histocompatibility Antigens; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase