The structure and functions of human lysophosphatidic acid acyltransferases

Front Biosci. 2001 Aug 1;6:D944-53. doi: 10.2741/leung.

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.

Publication types

  • Review

MeSH terms

  • Acyltransferases / chemistry
  • Acyltransferases / genetics*
  • Acyltransferases / physiology*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Chromosome Mapping
  • Cytokines / physiology
  • Escherichia coli / genetics
  • Histocompatibility Antigens / physiology
  • Humans
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Spodoptera / genetics
  • Tissue Distribution

Substances

  • Cytokines
  • Histocompatibility Antigens
  • Acyltransferases
  • 2-acylglycerophosphate acyltransferase