Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361824402> ?p ?o ?g. }
Showing items 1 to 78 of
78
with 100 items per page.
- W4361824402 abstract "<div>Abstract<p>Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia. Here, we studied the function of novel germline variants in CSF3R at amino acid N610. These N610 substitutions were potently oncogenic and activated the receptor independently of its ligand GCSF. These mutations activated the JAK–STAT signaling pathway and conferred sensitivity to JAK inhibitors. Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans. N610 was also the primary site of sialylation of the receptor. Membrane-proximal N-linked glycosylation was critical for maintaining the ligand dependence of the receptor. Mutation of the N610 site prevented membrane-proximal N-glycosylation of CSF3R, which then drove ligand-independent cellular expansion. Kinase inhibitors blocked growth of cells with an N610 mutation. This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation.</p>Significance:<p>This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia </p></div>" @default.
- W4361824402 created "2023-04-05" @default.
- W4361824402 creator A5002632381 @default.
- W4361824402 creator A5015789771 @default.
- W4361824402 creator A5025595346 @default.
- W4361824402 creator A5032163882 @default.
- W4361824402 creator A5053467487 @default.
- W4361824402 creator A5056839149 @default.
- W4361824402 creator A5063849472 @default.
- W4361824402 creator A5070941585 @default.
- W4361824402 creator A5073522080 @default.
- W4361824402 creator A5073577112 @default.
- W4361824402 creator A5082586608 @default.
- W4361824402 creator A5086626442 @default.
- W4361824402 creator A5088409133 @default.
- W4361824402 date "2023-03-31" @default.
- W4361824402 modified "2023-09-27" @default.
- W4361824402 title "Data from A Novel Germline Variant in CSF3R Reduces N-Glycosylation and Exerts Potent Oncogenic Effects in Leukemia" @default.
- W4361824402 doi "https://doi.org/10.1158/0008-5472.c.6510584.v1" @default.
- W4361824402 hasPublicationYear "2023" @default.
- W4361824402 type Work @default.
- W4361824402 citedByCount "0" @default.
- W4361824402 crossrefType "posted-content" @default.
- W4361824402 hasAuthorship W4361824402A5002632381 @default.
- W4361824402 hasAuthorship W4361824402A5015789771 @default.
- W4361824402 hasAuthorship W4361824402A5025595346 @default.
- W4361824402 hasAuthorship W4361824402A5032163882 @default.
- W4361824402 hasAuthorship W4361824402A5053467487 @default.
- W4361824402 hasAuthorship W4361824402A5056839149 @default.
- W4361824402 hasAuthorship W4361824402A5063849472 @default.
- W4361824402 hasAuthorship W4361824402A5070941585 @default.
- W4361824402 hasAuthorship W4361824402A5073522080 @default.
- W4361824402 hasAuthorship W4361824402A5073577112 @default.
- W4361824402 hasAuthorship W4361824402A5082586608 @default.
- W4361824402 hasAuthorship W4361824402A5086626442 @default.
- W4361824402 hasAuthorship W4361824402A5088409133 @default.
- W4361824402 hasConcept C108625454 @default.
- W4361824402 hasConcept C11960822 @default.
- W4361824402 hasConcept C170493617 @default.
- W4361824402 hasConcept C185592680 @default.
- W4361824402 hasConcept C206212055 @default.
- W4361824402 hasConcept C2777313579 @default.
- W4361824402 hasConcept C2778461978 @default.
- W4361824402 hasConcept C2778729363 @default.
- W4361824402 hasConcept C30324644 @default.
- W4361824402 hasConcept C502942594 @default.
- W4361824402 hasConcept C54355233 @default.
- W4361824402 hasConcept C86803240 @default.
- W4361824402 hasConcept C95444343 @default.
- W4361824402 hasConceptScore W4361824402C108625454 @default.
- W4361824402 hasConceptScore W4361824402C11960822 @default.
- W4361824402 hasConceptScore W4361824402C170493617 @default.
- W4361824402 hasConceptScore W4361824402C185592680 @default.
- W4361824402 hasConceptScore W4361824402C206212055 @default.
- W4361824402 hasConceptScore W4361824402C2777313579 @default.
- W4361824402 hasConceptScore W4361824402C2778461978 @default.
- W4361824402 hasConceptScore W4361824402C2778729363 @default.
- W4361824402 hasConceptScore W4361824402C30324644 @default.
- W4361824402 hasConceptScore W4361824402C502942594 @default.
- W4361824402 hasConceptScore W4361824402C54355233 @default.
- W4361824402 hasConceptScore W4361824402C86803240 @default.
- W4361824402 hasConceptScore W4361824402C95444343 @default.
- W4361824402 hasLocation W43618244021 @default.
- W4361824402 hasOpenAccess W4361824402 @default.
- W4361824402 hasPrimaryLocation W43618244021 @default.
- W4361824402 hasRelatedWork W1555877029 @default.
- W4361824402 hasRelatedWork W1988365462 @default.
- W4361824402 hasRelatedWork W2002528839 @default.
- W4361824402 hasRelatedWork W2020683762 @default.
- W4361824402 hasRelatedWork W2057984012 @default.
- W4361824402 hasRelatedWork W2065047355 @default.
- W4361824402 hasRelatedWork W2417600213 @default.
- W4361824402 hasRelatedWork W2611083600 @default.
- W4361824402 hasRelatedWork W4214886134 @default.
- W4361824402 hasRelatedWork W53433898 @default.
- W4361824402 isParatext "false" @default.
- W4361824402 isRetracted "false" @default.
- W4361824402 workType "article" @default.