Yeast carboxypeptidase Y vacuolar targeting signal is defined by four propeptide amino acids

TY - JOUR

T1 - Yeast carboxypeptidase Y vacuolar targeting signal is defined by four propeptide amino acids

AU - Valls, L A

AU - Winther, Jakob R.

AU - Stevens, T H

PY - 1990

Y1 - 1990

N2 - The amino-terminal propeptide of carboxypeptidase Y (CPY) is necessary and sufficient for targeting this glycoprotein to the vacuole of Saccharomyces cerevisiae. A 16 amino acid stretch of the propeptide was subjected to region-directed mutagenesis using randomized oligonucleotides. Mutations altering any of four contiguous amino acids, Gln-Arg-Pro-Leu, resulted in secretion of the encoded CPY precursor (proCPY), demonstrating that these residues form the core of the vacuolar targeting signal. Cells that simultaneously synthesize both wild-type and sorting-defective forms of proCPY efficiently sort and deliver only the wild-type molecule to the vacuole. These results indicate that the PRC1 missorting mutations are cis-dominant, implying that the mutant forms of proCPY are secreted as a consequence of failing to interact with the sorting apparatus, rather than a general poisoning of the vacuolar protein targeting system.

AB - The amino-terminal propeptide of carboxypeptidase Y (CPY) is necessary and sufficient for targeting this glycoprotein to the vacuole of Saccharomyces cerevisiae. A 16 amino acid stretch of the propeptide was subjected to region-directed mutagenesis using randomized oligonucleotides. Mutations altering any of four contiguous amino acids, Gln-Arg-Pro-Leu, resulted in secretion of the encoded CPY precursor (proCPY), demonstrating that these residues form the core of the vacuolar targeting signal. Cells that simultaneously synthesize both wild-type and sorting-defective forms of proCPY efficiently sort and deliver only the wild-type molecule to the vacuole. These results indicate that the PRC1 missorting mutations are cis-dominant, implying that the mutant forms of proCPY are secreted as a consequence of failing to interact with the sorting apparatus, rather than a general poisoning of the vacuolar protein targeting system.

KW - Amino Acid Sequence

KW - Base Sequence

KW - Carboxypeptidases

KW - Cathepsin A

KW - Cloning, Molecular

KW - Enzyme Precursors

KW - Genes, Fungal

KW - Glycoproteins

KW - Molecular Sequence Data

KW - Mutation

KW - Oligonucleotide Probes

KW - Phenotype

KW - Protein Processing, Post-Translational

KW - Restriction Mapping

KW - Saccharomyces cerevisiae

KW - Saccharomyces cerevisiae Proteins

KW - Vacuoles

M3 - Journal article

C2 - 2199455

SN - 0021-9525

VL - 111

SP - 361

EP - 368

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 2

ER -