title: Data on quantification of signaling pathways activated by KIT and PDGFRA mutants.
abstract: The present data are related to the article entitled "Insights into ligand stimulation effects on gastro-intestinal stromal tumors signaling" (C. Bahlawane, M. Schmitz, E. Letellier, K. Arumugam, N. Nicot, P.V. Nazarov, S. Haan, 2016) [1]. Constitutive and ligand-derived signaling pathways mediated by KIT and PDGFRA mutated proteins found in gastrointestinal stromal tumors (GIST) were compared. Expression of mutant proteins was induced by doxycycline in an isogenic background (Hek293 cells). Kit was identified by FACS at the cell surface and found to be quickly degraded or internalized upon SCF stimulation for both Kit Wild type and Kit mutant counterparts. Investigation of the main activated pathways in GIST unraveled a new feature specific for oncogenic KIT mutants, namely their ability to be further activated by Kit ligand, the stem cell factor (scf). We were also able to identify the MAPK pathway as the most prominent target for a common inhibition of PDGFRA and KIT oncogenic signaling. Western blotting and micro-array analysis were applied to analyze the capacities of the mutant to induce an effective STATs response. Among all Kit mutants, only Kit Ex11 deletion mutant was able to elicit an effective STATs response whereas all PDGFRA were able to do so.
authors.affiliation: Molecular Disease Mechanisms group, Life Sciences Research Unit, University of Luxembourg, Campus Belval, 6 Avenue du Swing, L-4367 Belvaux, Luxembourg.
authors.forename: Christelle
authors.initials: C
authors.lastname: Bahlawane
authors.affiliation: Molecular Disease Mechanisms group, Life Sciences Research Unit, University of Luxembourg, Campus Belval, 6 Avenue du Swing, L-4367 Belvaux, Luxembourg.
authors.forename: Martine
authors.initials: M
authors.lastname: Schmitz
authors.affiliation: Molecular Disease Mechanisms group, Life Sciences Research Unit, University of Luxembourg, Campus Belval, 6 Avenue du Swing, L-4367 Belvaux, Luxembourg.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Letellier
authors.affiliation: Department of Infection and Immunity, LIH, 84 Val Fleuri, L-1526 Luxembourg.
authors.forename: Karthik
authors.initials: K
authors.lastname: Arumugam
authors.affiliation: Genomics Research Unit, LIH, 84 Val Fleuri, L-1526 Luxembourg.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nicot
authors.affiliation: Genomics Research Unit, LIH, 84 Val Fleuri, L-1526 Luxembourg.
authors.forename: Petr V
authors.initials: PV
authors.lastname: Nazarov
authors.affiliation: Molecular Disease Mechanisms group, Life Sciences Research Unit, University of Luxembourg, Campus Belval, 6 Avenue du Swing, L-4367 Belvaux, Luxembourg.
authors.forename: Serge
authors.initials: S
authors.lastname: Haan
keywords: Gastro-intestinal stromal tumours; MAPK; PD0325901; PDGFRα; PI3K; Stem cell factor; c-KIT