Linked Life Data

1527091

Source:http://linkedlifedata.com/resource/pubmed/id/1527091

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
27
pubmed:dateCreated
1992-10-22
pubmed:abstractText
Human protein C (HPC) undergoes several post-translational modifications, including gamma-carboxylation, N-linked glycosylation, and internal proteolytic processing. We have utilized a recombinant human kidney cell line (293) secreting correctly modified HPC (rHPC) to study the processing reactions for the modification of this complex protein. gamma-Carboxylation was shown to proceed via a vitamin K-dependent pathway and was required for both efficient secretion and anticoagulant activity. rHPC was rapidly secreted following the addition of vitamin K to depleted cells, and secretion was not inhibited by cyclohexamide indicating that non gamma-carboxylated rHPC accumulates as an intracellular releasable pool. However, in cells grown in the presence of vitamin K, the majority of intracellular rHPC was gamma-carboxylated, suggesting that this post-translational modification is not rate limiting for secretion under conditions optimal for vitamin K-dependent carboxylation. Nonglycosylated rHPC was found to be secreted inefficiently, and processing of the N-linked core in the endoplasmic reticulum, but not in the Golgi, was required for secretion. Further, the intracellular rHPC present in vitamin K-supplemented cells was core glycosylated, but not processed past the high mannose step. gamma-Carboxylation occurred after core glycosylation, indicating that this modification is not cotranslational. Further, glycosylation and gamma-carboxylation were not coupled and did not need to proceed sequentially. Proteolytic processing of the internal KR dipeptide was found to occur late in the secretion pathway, and the cleavage was calcium-dependent. The secretion rate of rHPC was also calcium-dependent but was independent of the calcium effect on internal KR dipeptide removal, indicating that cleavage is not required for efficient secretion. Our results define the sequence of processing events, the subcellular localization of the processing reactions, and the rate-limiting steps in the secretion pathway for this complex protein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19710-7
pubmed:dateRevised
2000-12-18
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Post-translational processing events in the secretion pathway of human protein C, a complex vitamin K-dependent antithrombotic factor.
pubmed:affiliation
Department of Biotechnology, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285.
pubmed:publicationType
Journal Article