Differential signaling networks of Bcr–Abl p210 and p190 kinases in leukemia cells defined by functional proteomics

Reckel, Sina; Hamelin, Romain; Georgeon, Sandrine; Armand, Florence; Jolliet, Q; Chiappe, Diego; Moniatte, Marc; Hantschel, Oliver

doi:10.1038/leu.2017.36

Cited by 90 publications

(105 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, the tyrosine phosphorylated phospho-proteins observed by chemical rescue of R/A Abl were also detected in chemical rescue of Bcr-Abl. These findings are consistent with a hyperactivity of Bcr-Abl that has been previously reported 25–27 , which broadens its substrate portfolio versus Abl. In addition, our study reveals novel Abl-mediated tyrosine phosphorylation sites, including proteins involved in metabolism and transcription.…”

Section: Discussionsupporting

confidence: 91%

Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase

et al. 2018

View full text Add to dashboard Cite

Identifying direct substrates targeted by protein kinases is important in understanding cellular physiology and intracellular signal transduction. Mass-spectrometry based quantitative proteomics provides a powerful tool for comprehensively characterizing the downstream substrates of protein kinases. This approach is efficiently applied to receptor kinases which can be precisely, directly, and rapidly activated by some agent, such as a growth factor. However, non-receptor tyrosine kinase Abl lacks the experimental advantage of extracellular growth factors as immediate and direct stimuli. To circumvent this limitation, we combine a chemical rescue approach with quantitative phosphoproteomics to identify targets of Abl and their phosphorylation sites with enhanced temporal resolution. Both known and novel putative substrates are identified, presenting opportunities for studying unanticipated functions of Abl under physiological and pathological conditions.

show abstract

Section: Discussionsupporting

confidence: 91%

Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase

et al. 2018

View full text Add to dashboard Cite

show abstract

“…17,18 There were 467 biotinylated proteins identified only by BioSITe, representing a subset of biotinylated proteins that were missed by conventional on-bead digestion (Figure 1E). Importantly, 23% (110/467) of these proteins have more than two sites of biotinylation; however, the majority, 77% (359/467), of these proteins are represented by only one site of biotinylation, indicating that these could represent low abundant proteins or transient interactions only observable by BioSITe.…”

Section: Resultsmentioning

confidence: 99%

“…We found many differential interactors determined by our previous studies to be relevant for BCR-ABL p190- and p210-specific signaling pathways; these included the p210-enriched interactors of SHIP1, SHIP2, CBL, and UBASH3B (Supplementary Figure 2B) and the p190-enriched interactors of Wiskott–Aldrich Syndrome protein (WAS) and WAS/WASL-interacting protein family member 1 (Wipf1). 17,18 Our quantitative BioSITe analysis also led to the identification of potentially novel interactors that preferentially interacted either with p190 (e.g., SRSF protein kinase 2 (SRPK2) and BRCA1 associated protein (BRAP)) or with p210 (e.g., C-terminal src kinase (CSK) and PDGFA-associated protein 1 (PDAP1) (Figure 3B)). Interestingly, we did not previously identify CSK as a p210-specific interactor, although it was found to be hyperphosphorylated in cells expressing p210.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

BioSITe: A Method for Direct Detection and Quantitation of Site-Specific Biotinylation

et al. 2017

View full text Add to dashboard Cite

Biotin-based labeling strategies are widely employed to study protein-protein interactions, subcellular proteomes and post-translational modifications, as well as, used in drug discovery. While the high affinity of streptavidin for biotin greatly facilitates the capture of biotinylated proteins, it still presents a challenge, as currently employed, for the recovery of biotinylated peptides. Here we describe a strategy designated Biotinylation Site Identification Technology (BioSITe) for the capture of biotinylated peptides for LC−MS/MS analyses. We demonstrate the utility of BioSITe when applied to proximity-dependent labeling methods, APEX and BioID, as well as biotin-based click chemistry strategies for identifying O-GlcNAc-modified sites. We demonstrate the use of isotopically labeled biotin for quantitative BioSITe experiments that simplify differential interactome analysis and obviate the need for metabolic labeling strategies such as SILAC. Our data also highlight the potential value of site-specific biotinylation in providing spatial and topological information about proteins and protein complexes. Overall, we anticipate that BioSITe will replace the conventional methods in studies where detection of biotinylation sites is important.

show abstract

“…While p210 is the hallmark of chronic myelogenous leukemia, p190 occurs in the majority of Ph + B‐ALL. It is intriguing that, very recently, marked differences in the interactome and tyrosine phosphoproteome of p190 and p210 Bcr‐Abl isoforms were found (Cutler et al, ; Reckel et al, ). Besides other aspects, these findings could give important indications regarding differential sensitivity to kinase inhibitors and other targeted agents.…”

Section: Introductionmentioning

confidence: 99%

Targeting the phosphatidylinositol 3‐kinase/Akt/mechanistic target of rapamycin signaling pathway in B‐lineage acute lymphoblastic leukemia: An update

Simioni

Martelli

Zauli

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15-20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease. Moreover, activation of this signaling cascade portends a poorer prognosis in both pediatric and adult B-ALL patients. Promising preclinical data on PI3K/Akt/mTOR inhibitors have documented their anticancer activity in B-ALL and some of these novel drugs have entered clinical trials as they could lead to a longer event-free survival and reduce therapy-associated toxicity for patients with B-ALL. This review highlights the current status of PI3K/Akt/mTOR inhibitors in B-ALL, with an emphasis on emerging evidence of the superior efficacy of synergistic combinations involving the use of traditional chemotherapeutics or other novel, targeted agents.

show abstract

Differential signaling networks of Bcr–Abl p210 and p190 kinases in leukemia cells defined by functional proteomics

Cited by 90 publications

References 43 publications

Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase

Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase

BioSITe: A Method for Direct Detection and Quantitation of Site-Specific Biotinylation

Targeting the phosphatidylinositol 3‐kinase/Akt/mechanistic target of rapamycin signaling pathway in B‐lineage acute lymphoblastic leukemia: An update

Contact Info

Product

Resources

About