MOLECULAR-CLONING, CHARACTERIZATION, AND DIFFERENTIAL EXPRESSION PATTERN OF MOUSE LUNG SURFACTANT CONVERTASE

We recently reported the purification and partial amino acid sequence of ''surfactant convertase,'' a 72-kDa glycoprotein involved in the ex tracellular metabolism of lung surfactant (S. Krishnasamy, N. J. Gross , A. L. Teng, R. M. Schultz, and R. Dhand. Biochem. Biophys. Res. Comm un. 235: 180-184, 1997). We report here the isolation of a cDNA clone encoding putative convertase from a mouse lung cDNA library. The cDNA spans a 1,836-bp sequence, with an open reading frame encoding 536 ami no acid residues in the mature protein and an 18-amino acid signal pep tide at the NH2 terminus. The deduced amino acid sequence matches the four partial amino acid sequences (68 residues) that were previously o btained from the purified protein. The deduced amino acid sequence con tains an 18-amino acid residue signal peptide, a serine active site co nsensus sequence, a histidine consensus sequence, five potential N-lin ked glycosylation sites, and a COOH-terminal secretory-type sequence H is-Thr-Glu-His-Lys. Primer-extension analysis revealed that transcript ion starts 29 nucleotides upstream from the start codon. Northern blot analysis of RNA isolated from various mouse organs showed that conver tase is expressed in lung, kidney, and liver as a 1,800-nucleotide-lon g transcript. The nucleotide and amino acid sequences of putative conv ertase are 98% homologous with mouse liver carboxylesterase. It thus m ay be the first member of the carboxylesterase family (EC 3.1.1.1)to b e expressed in lung parenchyma and the first with a known physiologica l function.