Facultative polypeptide translocation allows a single mRNA to encode the secreted and cytosolic forms of plasminogen activators inhibitor 2.
Two forms of plasminogen activators inhibitor 2 (PAI-2) are synthesized by human and murine monocytes/macrophages: one accumulates in the cytosol, while the other is translocated into the endoplasmic reticulum, glycosylated and secreted. We show here that a single mRNA encodes both forms of PAI-2. Firstly, a single PIA-2 mRNA was detected by Northern blot hybridization and by RNase protection. Secondly, transfection of a PAI-2 cDNA led to the synthesis of both forms of PAI-2. Finally, in vitro translation of an mRNA transcript of the PAI-2 cDNA in the presence of microsomal membranes generated two topologically distinct forms of PAI-2. The cytosolic and secreted forms of PAI-2 do not result from the use of two translation start sites, since their synthesis initiates at the same AUG, in a sequence context that is conserved between the human and murine genes. Thus, the accumulation of one polypeptide into two topologically distinct cellular compartments can be achieved by facultative translocation.
Belin
D
D
Département de Pathologie, University of Geneva Medical Center, Switzerland.
Wohlwend
A
A
Schleuning
W D
WD
Kruithof
E K
EK
Vassalli
J D
JD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D015152:Blotting, Northern; D002458:Cell Fractionation; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000378:metabolism*; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D012260:Ribonucleases / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D012769:Shock; D014162:Transfection
D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D012260:Ribonucleases