The molecular basis for the aberrant production of plasminogen activator inhibitor type 2 in THP-1 monocytes
Details
Serval ID
serval:BIB_6E8D98A7CE76
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The molecular basis for the aberrant production of plasminogen activator inhibitor type 2 in THP-1 monocytes
Journal
Thrombosis and Haemostasis
ISSN
0340-6245 (Print)
Publication state
Published
Issued date
09/2000
Volume
84
Number
3
Pages
468-73
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Research Support, Non-U.S. Gov't --- Old month value: Sep
Abstract
Plasminogen activator inhibitor type 2 (PAI-2) is a urokinase inhibitor that is expressed primarily in monocytes. THP-1 monocytes, however. contain a unique defect in the production of PAI-2 in that the PAI-2 transcript is truncated and the expressed protein inactive (1). Here we describe the basis of this mutation in THP-1 cells. Southern blot analysis of THP-1-derived genomic DNA indicated that there were no obvious deletions in the structure of the PAI-2 gene. However, assessment of the THP-1-derived PAI-2 transcript by RT-PCR indicated that only exons seven and eight of the normal PAI-2 mRNA could be detected. Cloning of the 5' region of the PAI-2 mRNA by 5-'RACE indicated that the PAI-2 cDNA derived from THP-1 cells is approximately 1329 bp long and contains 180 bp of sequence derived from intron 5. followed by sequences corresponding to exons seven and eight of the normal PAI-2 mRNA. The presence of the intron five fragment in endogenous THP-1 derived PAI-2 mRNA was confirmed by Northern blotting. The absence of any wild-type PAI-2 mRNA in these cells suggests that one copy of the PAI-2 allele has been deleted. The remaining allele producing the truncated mRNA appears to have undergone a translocation event and contains a mutation that has disrupted the splicing of the PAI-2 primary transcript.
Keywords
Cloning, Molecular
Exons
Humans
Introns
Monocytes/*metabolism
Mutation
Plasminogen Activator Inhibitor 2/genetics/*metabolism
RNA, Messenger/chemistry/genetics
Sequence Analysis, RNA
Translocation, Genetic
Tumor Cells, Cultured
U937 Cells
Pubmed
Web of science
Create date
25/01/2008 15:19
Last modification date
20/08/2019 15:27