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A novel hormone-sensitive lipase isoform expressed in pancreatic beta -cells.

Lindvall, Håkan LU ; Nevsten, Pernilla LU ; Ström, Kristoffer LU ; Wallenberg, Reine LU ; Sundler, Frank LU ; Langin, Dominique; Sörhede Winzell, Maria LU and Holm, Cecilia LU (2004) In Journal of Biological Chemistry 279(5). p.3828-3836
Abstract
Hormone-sensitive lipase (HSL) is a key enzyme in fatty acid mobilization in many cell types. Two isoforms of HSL are known to date, namely HSLadi (84 kDa in rat) and HSLtes (130 kDa in rat). These are encoded by the same gene, with exons 1-9 encoding the parts that are common to both and an additional 5'-exon encoding the additional amino acids in HSLtes. HSL of various tissues, among these the islet of Langerhans, is larger than HSLadi, but not as large as HSLtes, indicating that there may be other 5'-coding exons. Here we describe the molecular basis for a novel 89-kDa HSL isoform that is expressed in -cells, adipocytes, adrenal glands, and ovaries in the rat and that is encoded by exons 1-9 and exon A, which is spliced to exon 1 and... (More)
Hormone-sensitive lipase (HSL) is a key enzyme in fatty acid mobilization in many cell types. Two isoforms of HSL are known to date, namely HSLadi (84 kDa in rat) and HSLtes (130 kDa in rat). These are encoded by the same gene, with exons 1-9 encoding the parts that are common to both and an additional 5'-exon encoding the additional amino acids in HSLtes. HSL of various tissues, among these the islet of Langerhans, is larger than HSLadi, but not as large as HSLtes, indicating that there may be other 5'-coding exons. Here we describe the molecular basis for a novel 89-kDa HSL isoform that is expressed in -cells, adipocytes, adrenal glands, and ovaries in the rat and that is encoded by exons 1-9 and exon A, which is spliced to exon 1 and thereby introducing an upstream start codon. The additional 5'-base pairs encode a 43-amino acid peptide, which is highly positively charged. Conglomerates of HSL molecules are in close association with the secretory granules of the -cell, as determined by immunoelectron microscopy with antibodies targeting two separate regions of HSL. We have also determined that the human genomic sequence upstream of exon A has promoter activity in INS-1 cells as well as glucose sensing capability, mediating an increase in expression at high glucose concentration. The minimal promoter is present within 170 bp from the transcriptional start site and maximal glucose responsiveness is conferred by sequence within 850 bp from the transcriptional start site. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
279
issue
5
pages
3828 - 3836
publisher
ASBMB
external identifiers
  • wos:000188379600085
  • pmid:14576146
  • scopus:0942265525
ISSN
1083-351X
DOI
10.1074/jbc.M311365200
language
English
LU publication?
yes
id
2c0de301-c201-4ad7-806f-739e78d24011 (old id 118215)
date added to LUP
2007-07-13 14:09:48
date last changed
2017-01-01 05:12:09
@article{2c0de301-c201-4ad7-806f-739e78d24011,
  abstract     = {Hormone-sensitive lipase (HSL) is a key enzyme in fatty acid mobilization in many cell types. Two isoforms of HSL are known to date, namely HSLadi (84 kDa in rat) and HSLtes (130 kDa in rat). These are encoded by the same gene, with exons 1-9 encoding the parts that are common to both and an additional 5'-exon encoding the additional amino acids in HSLtes. HSL of various tissues, among these the islet of Langerhans, is larger than HSLadi, but not as large as HSLtes, indicating that there may be other 5'-coding exons. Here we describe the molecular basis for a novel 89-kDa HSL isoform that is expressed in -cells, adipocytes, adrenal glands, and ovaries in the rat and that is encoded by exons 1-9 and exon A, which is spliced to exon 1 and thereby introducing an upstream start codon. The additional 5'-base pairs encode a 43-amino acid peptide, which is highly positively charged. Conglomerates of HSL molecules are in close association with the secretory granules of the -cell, as determined by immunoelectron microscopy with antibodies targeting two separate regions of HSL. We have also determined that the human genomic sequence upstream of exon A has promoter activity in INS-1 cells as well as glucose sensing capability, mediating an increase in expression at high glucose concentration. The minimal promoter is present within 170 bp from the transcriptional start site and maximal glucose responsiveness is conferred by sequence within 850 bp from the transcriptional start site.},
  author       = {Lindvall, Håkan and Nevsten, Pernilla and Ström, Kristoffer and Wallenberg, Reine and Sundler, Frank and Langin, Dominique and Sörhede Winzell, Maria and Holm, Cecilia},
  issn         = {1083-351X},
  language     = {eng},
  number       = {5},
  pages        = {3828--3836},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {A novel hormone-sensitive lipase isoform expressed in pancreatic beta -cells.},
  url          = {http://dx.doi.org/10.1074/jbc.M311365200},
  volume       = {279},
  year         = {2004},
}