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PMID:14766755

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Citation

Ueno, T, Linder, S, Na, CL, Rice, WR, Johansson, J and Weaver, TE (2004) Processing of pulmonary surfactant protein B by napsin and cathepsin H. J. Biol. Chem. 279:16178-84

Abstract

Surfactant protein B (SP-B) is an essential constituent of pulmonary surfactant. SP-B is synthesized in alveolar type II cells as a preproprotein and processed to the mature peptide by the cleavage of NH2- and COOH-terminal peptides. An aspartyl protease has been suggested to cleave the NH2-terminal propeptide resulting in a 25-kDa intermediate. Napsin, an aspartyl protease expressed in alveolar type II cells, was detected in fetal lung homogenates as early as day 16 of gestation, 1 day before the onset of SP-B expression and processing. Napsin was localized to multivesicular bodies, the site of SP-B proprotein processing in type II cells. Incubation of SP-B proprotein from type II cells with a crude membrane extract from napsin-transfected cells resulted in enhanced levels of a 25-kDa intermediate. Purified napsin cleaved a recombinant SP-B/EGFP fusion protein within the NH2-terminal propeptide between Leu178 and Pro179, 22 amino acids upstream of the NH2 terminus of mature SP-B. Cathepsin H, a cysteine protease also implicated in pro-SP-B processing, cleaved SP-B/EGFP fusion protein 13 amino acids upstream of the NH2 terminus of mature SP-B. Napsin did not cleave the COOH-terminal peptide, whereas cathepsin H cleaved the boundary between mature SP-B and the COOH-terminal peptide and at several other sites within the COOH-terminal peptide. Knockdown of napsin by small interfering RNA resulted in decreased levels of mature SP-B and mature SP-C in type II cells. These results suggest that napsin, cathepsin H, and at least one other enzyme are involved in maturation of the biologically active SP-B peptide.

Links

PubMed Online version:10.1074/jbc.M312029200

Keywords

Animals; Aspartic Acid Endopeptidases/metabolism; Cathepsin H; Cathepsins/metabolism; Cells, Cultured; Cysteine Endopeptidases/metabolism; Humans; Kidney/metabolism; Kidney/ultrastructure; Lung/metabolism; Lung/ultrastructure; Mice; Protein Processing, Post-Translational; Pulmonary Surfactant-Associated Protein B/metabolism; Recombinant Fusion Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:NAPSA

involved_in

GO:0033619: membrane protein proteolysis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P50405)

Seeded From UniProt

complete

MOUSE:NAPSA

located_in

GO:0097208: alveolar lamellar body

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000082)

Seeded From UniProt

complete

MOUSE:NAPSA

enables

GO:0004175: endopeptidase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:NAPSA

located_in

GO:0005764: lysosome

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0002518)|part_of:(CL:0000583)

Seeded From UniProt

complete

HUMAN:NAPSA

involved_in

GO:0033619: membrane protein proteolysis

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P07988)

Seeded From UniProt

complete

HUMAN:NAPSA

enables

GO:0004175: endopeptidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:NAPSA

located_in

GO:0005764: lysosome

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0002518)

Seeded From UniProt

complete

HUMAN:CATH

involved_in

GO:0033619: membrane protein proteolysis

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P07988)

Seeded From UniProt

complete

HUMAN:CATH

enables

GO:0004175: endopeptidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:CATH

involved_in

GO:0033619: membrane protein proteolysis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P50405)

Seeded From UniProt

complete

MOUSE:CATH

enables

GO:0004175: endopeptidase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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