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Differential activity of c-KIT splice forms is controlled by extracellular peptide insert length.

Phung, Bengt LU ; Steingrímsson, Eiríkur and Rönnstrand, Lars LU (2013) In Cellular Signalling 25(11). p.2231-2238
Abstract
Understanding receptor activation is important for disease intervention. Activation of the receptor tyrosine kinase c-KIT is involved in numerous diseases including melanoma, mastocytosis, multiple myeloma and gastrointestinal stromal tumors. To better understand the regulation of activation, we studied the two c-KIT isoforms, c-KIT(-) and c-KIT(+) which differ by a tetrapeptide insert GNNK, located in the extracellular juxtamembrane domain of the c-KIT(+) isoform. This region is important for regulating receptor activation. Here we show that the consecutive elimination of one amino acid at a time from the GNNK tetrapeptide insert gradually increases receptor tyrosine phosphorylation, ubiquitination, internalization and downstream MAP... (More)
Understanding receptor activation is important for disease intervention. Activation of the receptor tyrosine kinase c-KIT is involved in numerous diseases including melanoma, mastocytosis, multiple myeloma and gastrointestinal stromal tumors. To better understand the regulation of activation, we studied the two c-KIT isoforms, c-KIT(-) and c-KIT(+) which differ by a tetrapeptide insert GNNK, located in the extracellular juxtamembrane domain of the c-KIT(+) isoform. This region is important for regulating receptor activation. Here we show that the consecutive elimination of one amino acid at a time from the GNNK tetrapeptide insert gradually increases receptor tyrosine phosphorylation, ubiquitination, internalization and downstream MAP kinase-ERK activation. Successively decreasing the insert length progressively improves cell survival during drug treatment. Our results indicate that the length of the tetrapeptide fine-tunes receptor activity, thus providing deeper insight into c-KIT activation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cellular Signalling
volume
25
issue
11
pages
2231 - 2238
publisher
Elsevier
external identifiers
  • wos:000324971800016
  • pmid:23880320
  • scopus:84882652190
  • pmid:23880320
ISSN
1873-3913
DOI
10.1016/j.cellsig.2013.07.011
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
id
4dd6b8a0-9658-400d-9910-4b56c87ad636 (old id 3955628)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23880320?dopt=Abstract
date added to LUP
2016-04-01 11:04:25
date last changed
2020-01-12 07:00:08
@article{4dd6b8a0-9658-400d-9910-4b56c87ad636,
  abstract     = {Understanding receptor activation is important for disease intervention. Activation of the receptor tyrosine kinase c-KIT is involved in numerous diseases including melanoma, mastocytosis, multiple myeloma and gastrointestinal stromal tumors. To better understand the regulation of activation, we studied the two c-KIT isoforms, c-KIT(-) and c-KIT(+) which differ by a tetrapeptide insert GNNK, located in the extracellular juxtamembrane domain of the c-KIT(+) isoform. This region is important for regulating receptor activation. Here we show that the consecutive elimination of one amino acid at a time from the GNNK tetrapeptide insert gradually increases receptor tyrosine phosphorylation, ubiquitination, internalization and downstream MAP kinase-ERK activation. Successively decreasing the insert length progressively improves cell survival during drug treatment. Our results indicate that the length of the tetrapeptide fine-tunes receptor activity, thus providing deeper insight into c-KIT activation.},
  author       = {Phung, Bengt and Steingrímsson, Eiríkur and Rönnstrand, Lars},
  issn         = {1873-3913},
  language     = {eng},
  number       = {11},
  pages        = {2231--2238},
  publisher    = {Elsevier},
  series       = {Cellular Signalling},
  title        = {Differential activity of c-KIT splice forms is controlled by extracellular peptide insert length.},
  url          = {http://dx.doi.org/10.1016/j.cellsig.2013.07.011},
  doi          = {10.1016/j.cellsig.2013.07.011},
  volume       = {25},
  year         = {2013},
}