Shedding of membrane epithin is blocked without LDLRA4 and its protease activation site.
Epithin, a mouse type II transmembrane serine protease, is processed at Gly149 and released from the membrane. Here, we report the identification of an epithin isoform, epithin(Delta), containing a 66 amino acid deletion from the full-length epithin, which is missing the 4th LDLRA domain and the protease activation sequence. This truncated isoform showed the same characteristic N-terminal processing at Gly149 as the full-length form, however, no protease activity was detected. The N-terminal processed epithin(Delta) short form (Epi(Delta)-S) was not released into the medium under conditions in which the processed epithin short form (Epi-S) is released. This type of epithin shedding was also prevented when serine protease inhibitors were added to cells expressing the full-length form. These results strongly suggest that the serine protease activity is involved in the shedding process. The presence of epithin(Delta) message was detected in multiple tissues and its significance is discussed.
Cho
Eun-Gyung
EG
Laboratory of Cellular and Molecular Immunology, NIAID, NIH, Bethesda, MD 20892-0420, USA.
Schwartz
Ronald H
RH
Kim
Moon G
MG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D023281:Genomics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; C467801:matriptase 2; C118992:St14 protein, mouse