The lysosomal proenzyme receptor that binds procathepsin L to microsomal membranes at pH 5 is a 43-kDa integral membrane protein.
Two lysosomal proenzymes, procathepsins L and D, bind to mouse fibroblast microsomal membranes at acidic pH. This membrane association is independent of the mannose-6-phosphate receptors and requires the presence of the N-terminal propeptides of the enzymes. We have identified the protein that specifically binds procathepsin L at pH 5. A 43-kDa membrane protein coimmunoprecipitated with procathepsin L at pH 5 but not at pH 7 when cells were denatured with detergents. Similarly, a 43-kDa integral membrane protein bound procathepsin L in three kinds of ligand blots at pH 5 but not at pH 7. A synthetic peptide containing the 24 N-terminal residues of mouse procathepsin L blocked the binding of procathepsin L to this integral membrane protein on ligand blots. These results indicate that the 43-kDa integral membrane protein is a lysosomal proenzyme receptor that specifically binds the procathepsin L activation peptide at acidic pH.
McIntyre
G F
GF
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599.
Erickson
A H
AH
D000818:Animals; D001667:Binding, Competitive; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D002460:Cell Line; D004792:Enzyme Precursors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D008024:Ligands; D008247:Lysosomes / Q000201:enzymology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D008970:Molecular Weight; D011485:Protein Binding
D004792:Enzyme Precursors; D008024:Ligands; D008565:Membrane Proteins; D002403:Cathepsins; C063905:procathepsin L; D056668:Cathepsin L