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A C‐terminal domain, which prevents secretion of the neuroendocrine protein 7B2 in Saccharomyces cerevisiae , inhibits Kex2 yet is processed by the Yap3 protease
Author(s) -
Chaudhuri Bhabatosh,
Stephan Christine
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00360-l
Subject(s) - secretion , saccharomyces cerevisiae , protease , biology , yeast , biochemistry , prohormone convertase , prohormone , enzyme , hormone
Recent reports reveal that the C‐terminal half of the neuroendocrine polypeptide 7B2 selectively inhibits and binds PC2, a mammalian prohormone converting enzyme that is homologous to the yeast pro‐α‐factor processing protease Kex2. During attempted secretion of the 185 amino‐acid human 7B2 in Saccharomyces cerevisiae , we observe that the protein is mostly retained inside the cell. However a mutant polypeptide (7B2Δ1), where the C‐terminal 48 amino acids of 7B2 are deleted, is efficiently secreted. Two shorter C‐terminal truncations either permit poor secretion or no secretion at all. Surprisingly, full‐length 7B2 but not 7B2Δ1 abolishes the catalytic activity of Kex2, indicating that C‐terminal residues of 7B2 might also be important for inhibition of the yeast protease. When the KEX 2 gene is disrupted, yeast cells unexpectedly secrete a 7B2 variant similar in size to 7B2Δ1, suggesting involvement of the alternate yeast prohormone convertase Yap3 in processing. Secretion is enhanced by overexpression of Yap3 and by the presence of a Lys‐Arg residue at the processing site of precursor 7B2. These results purport that, in neuroendocrine cells too, secretion of 7B2 could be mediated by a homologue of Yap3.