Differential activity of c-KIT splice forms is controlled by extracellular peptide insert length.
Författare
Summary, in English
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.
Avdelning/ar
- Institutionen för translationell medicin
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2013
Språk
Engelska
Sidor
2231-2238
Publikation/Tidskrift/Serie
Cellular Signalling
Volym
25
Issue
11
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Microbiology
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1873-3913