Dataset Information

Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/PI3K/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia

ABSTRACT: Mutations in the interleukin-7 receptor (IL7R) or the JAK3 kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here, we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells and human JAK3 mutated T-ALL samples. Novel peptides shown to be downstream of mutant JAK3 regulating RNA metabolism as well as epigenetic and apoptotic processes were validated using targeted PRM proteomics.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606) Mus Musculus (ncbitaxon:10090)

SUBMITTER: Dr. Matt Dun

PROVIDER: MSV000081327 | MassIVE | Fri Jul 14 01:58:00 BST 2017

SECONDARY ACCESSION(S): PXD007046

REPOSITORIES: MassIVE

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Publications

Heterogeneity in the structural basis of the human complement C4A null allele (C4A Q0) as revealed by HindIII restriction fragment length polymorphism analysis.

Uring-Lambert B B Vegnaduzzi N N Carroll M C MC Tongio M M MM Goetz J J Hauptmann G G

FEBS letters 19870601 1

The highly polymorphic fourth component of human complement (C4) is usually encoded by two genes. C4A and C4B, adjacent to the 21-hydroxylase (21-OH) genes, 21-OHA and 21-OHB, and is also remarkable in the high frequency of the 'null' alleles, C4A Q0 and C4B Q0. The molecular basis for the C4A Q0 allele was studied in 26 families through restriction fragment length polymorphism (RFLP) analysis with C4 and 21-OH cDNA probes after digestion of the DNA with the endonuclease HindIII. The individuals ...[more]

PMID: 2885219

Publication: 1/2

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