Transmembrane orientation of glycoproteins encoded by the v-fms oncogene.
The retroviral oncogene v-fms encodes a glycoprotein whose transport to the plasma membrane is required for transformation. Tryptic digestion of microsomes from transformed cells yielded membrane-protected amino-terminal fragments 40 kd smaller than intact molecules. These fragments were glycosylated, and they included v-fms-coded epitopes expressed at the cell surface. Deletion of the predicted membrane-spanning peptide generated polypeptides that were completely sequestered within microsomes. The mutant glycoproteins acquired more asparagine-linked oligosaccharide chains than did wild-type molecules, lacked kinase activity in vitro, were not transported to the cell surface, and had no transforming activity. Thus, the membrane-spanning segment in the middle of the glycoprotein interrupts translocation of nascent chains into the endoplasmic reticulum, ultimately orienting the amino-terminal domain outside the cell and the carboxy-terminal kinase domain in the cytoplasm. These topological features are similar to those of several growth factor receptors, suggesting that v-fms transforms cells through modified receptor-mediated signals.
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002472:Cell Transformation, Viral; D003593:Cytoplasm / Q000378:metabolism; D004622:Embryo, Mammalian; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney; D008168:Lung; D008861:Microsomes / Q000378:metabolism; D008907:Mink; D009857:Oncogenes; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D012190:Retroviridae / Q000235:genetics*; D014357:Trypsin / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D006023:Glycoproteins; D010446:Peptide Fragments; D014764:Viral Proteins; D014357:Trypsin