TY - JOUR
T1 - Importance of the propeptide sequence of human preproparathyroid hormone for signal sequence function
AU - Wiren, K. M.
AU - Potts, J. T.
AU - Kronenberg, H. M.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1988
Y1 - 1988
N2 - The function of amino-terminal pro-specific peptides (propeptides), sequences often found on intermediate precursor forms of secreted proteins, is poorly understood. Human preproparathyroid hormone (prepro-PTH), a precursor protein containing such a propeptide, is initially synthesized as a precursor containing a 25-amino acid signal sequence, a 6-amino acid propeptide, and the 84-amino acid mature secreted peptide. Cloned cDNA encoding prepro-PTH and synthetic oligonucleotides were used to generate a mutant missing precisely the pro-specific sequences. The effects of this deletion on signal sequence function and on secretion per se were assessed after expression of the mutant cDNA in intact cells and in a cell-free translation system using synthetic mRNA in the presence of microsomal membranes. The mutant precursor protein was inefficiently translocated and cleaved, and cleavage occcurred both at the normal site and within the signal sequence. Thus, for the eukaryotic protein prepro-PTH, sequences immediately downstream and separate from the classically defined signal sequence facilitate accurate and efficient signal function.
AB - The function of amino-terminal pro-specific peptides (propeptides), sequences often found on intermediate precursor forms of secreted proteins, is poorly understood. Human preproparathyroid hormone (prepro-PTH), a precursor protein containing such a propeptide, is initially synthesized as a precursor containing a 25-amino acid signal sequence, a 6-amino acid propeptide, and the 84-amino acid mature secreted peptide. Cloned cDNA encoding prepro-PTH and synthetic oligonucleotides were used to generate a mutant missing precisely the pro-specific sequences. The effects of this deletion on signal sequence function and on secretion per se were assessed after expression of the mutant cDNA in intact cells and in a cell-free translation system using synthetic mRNA in the presence of microsomal membranes. The mutant precursor protein was inefficiently translocated and cleaved, and cleavage occcurred both at the normal site and within the signal sequence. Thus, for the eukaryotic protein prepro-PTH, sequences immediately downstream and separate from the classically defined signal sequence facilitate accurate and efficient signal function.
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M3 - Article
C2 - 3198649
AN - SCOPUS:0024230299
SN - 0021-9258
VL - 263
SP - 19771
EP - 19777
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 36
ER -