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Cloning and Functional Characterization of a Rat Lung LysoPC Acyltransferase
Author(s) -
Chen Xueni,
Bridges James P.,
Shan John,
Mason Robert J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a551-a
Subject(s) - acyltransferase , phospholipid , dipalmitoylphosphatidylcholine , pulmonary surfactant , biochemistry , chemistry , biosynthesis , phospholipid transfer protein , microbiology and biotechnology , biology , phosphatidylcholine , enzyme , membrane
Pulmonary surfactant is a complex of lipids and proteins produced by alveolar type II cells that provides the low surface tension at the air‐liquid interface. The phospholipid most responsible for providing the low surface tension in the lung is dipalmitoylphosphatidylcholine (DPPC). DPPC is synthesized in large part by PC remodeling, and a lysophosphatidylcholine (lysoPC) acyltransferase is thought to play a critical role in its synthesis. However, this acyltransferase has not yet been identified. We have cloned full‐length rat and mouse cDNAs coding for a novel lysoPC acyltransferase (LPCAT). When transfected into COS‐7 cells and HEK293 cells, LPCAT significantly increased lysoPC acyltransferase activity. LPCAT preferred palmitoyl‐CoA to oleoyl‐CoA as the acyl donor. Mutation of a histidine residue in the putative catalytic domain completely abolished acyltransferase activity. This LPCAT was preferentially expressed in the lung, specifically within alveolar type II cells. Expression in the fetal lung and in rat type II cells correlated with the expression of the surfactant proteins. LPCAT expression in alveolar type II cells was stimulated by keratinocyte growth factors (KGF). We hypothesize that LPCAT plays a critical role in regulating surfactant phospholipid biosynthesis and suggest that understanding the regulation of LPCAT will offer important insight into surfactant phospholipid biosynthesis. This work was supported by NIH grants H2‐29891 and HL‐56387