Differential activity of c-KIT splice forms is controlled by extracellular peptide insert length.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3955628
- author
- Phung, Bengt LU ; Steingrímsson, Eiríkur and Rönnstrand, Lars LU
- organization
- publishing date
- 2013
- 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
- 2022-01-26 05:10:43
@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}}, }