SHP1 Protein Tyrosine Phosphatase Negatively Modulates Erythroid Differentiation and Suppression of Apoptosis in J2E Erythroleukemic Cells

Bittorf, Thomas; Seiler, Jens; Jaster, Robert; Brock, Josef

doi:10.1515/bc.1999.152

Cited by 36 publications

(29 citation statements)

References 62 publications

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“…Inspection of quadrant eight reveals that the point mutant preferentially activates proteins involved in immune system signaling. For example, Tec and Shp1 are both critical mediators of normal hematopoiesis [27,28] and, when dysregulated, may contribute to leukemogenesis [29,30]. These and other proteins listed in 1432 ZHANG ET AL.…”

Section: Quantitative Phosphoproteomic Analysis Of Flt-3 Signaling Inmentioning

confidence: 99%

Optimized orbitrap HCD for quantitative analysis of phosphopeptides

Zhang

Ficarro

et al. 2009

J. Am. Soc. Mass Spectrom.

118

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Despite the tremendous commercial success of radio frequency quadrupole ion traps for bottom-up proteomics studies, there is growing evidence that peptides decorated with labile post-translational modifications are less amenable to low-energy, resonate excitation MS/MS analysis. Moreover, multiplexed stable isotope reagents designed for MS/MSbased quantification of peptides rely on accurate and robust detection of low-mass fragments for all precursors. Collectively these observations suggest that beam-type or tandem in-space MS/MS measurements, such as that available on traditional triple quadrupole mass spectrometers, may provide beneficial figures of merit for quantitative proteomics analyses. The recent introduction of a multipole collision cell adjacent to an Orbitrap mass analyzer provides for higher energy collisionally activated dissociation (HCD) with efficient capture of fragment ions over a wide mass range. Here we describe optimization of various instrument and post-acquisition parameters that collectively provide for quantification of iTRAQ-labeled phosphorylated peptides isolated from complex cell lysates. Peptides spanning a concentration dynamic range of 100:1 are readily quantified. Our results indicate that appropriate parameterization of collision energy as a function of precursor m/z and z provides for optimal performance in terms of peptide identification and relative quantification by iTRAQ. Using this approach, we readily identify activated signaling pathways downstream of oncogenic mutants of Flt-3 kinase in a model system of human myeloid leukemia. [4][5][6], extended mass range capability [7], use of helium buffer gas [3], and automated control of trapped ion populations [8], all combined to catapult trap-based instruments to the forefront of proteomics research. Concomitant advances in CPU and embedded systems provided for rapid and automated control of instrument parameters and yielded heretofore unattainable throughput for peptide sequence analysis via LC-MS/MS. Today, several years past the emergence of proteomics as a field of active research [9], it is clear that "typical" tryptic peptides are very amenable to sequence analysis via low-energy MS/MS. More recently, the introduction of hybrid geometries [10 -12] and other instrument configurations [13,14], along with protocols for enrichment of post-translationally modified peptides [15,16], have dramatically increased the experimental dynamic range of proteomics analyses. Collectively, these results have revealed that peptides decorated with labile modifications often are not well behaved under low-energy MS/MS conditions. For example, facile loss of phosphoric acid from the side chains of serine-and threoninephosphorylated peptides often limits the available sequence-specific information contained in associated MS/MS spectra [17,18]. Interestingly, recent reports [19,20] suggest that higher energy, or "triple quadrupole like," MS/MS can provide improved sequence analysis, particularly for phosphorylated peptides. In the work repo...

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Section: Quantitative Phosphoproteomic Analysis Of Flt-3 Signaling Inmentioning

confidence: 99%

Optimized orbitrap HCD for quantitative analysis of phosphopeptides

Zhang

Ficarro

et al. 2009

J. Am. Soc. Mass Spectrom.

118

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“…Similarly, PTPeC, has been shown to inhibit JAK kinase phosphorylation resulting in inhibition of di erentiation and apoptosis in M1 cells stimulated by IL-6 and LIF (Tanuma et al, 2000). Bittorf et al (1999) recently showed that SHP1 inhibited erythropoietin-induced erythroid di erentiation and inhibition of apoptosis in an erythroleukemic cell line. This e ect of SHP1 was a result of inhibition of both the JAK kinase and MAP kinase pathways.…”

Section: Negative Regulation By Protein Tyrosine Phosphatasesmentioning

confidence: 99%

Janus kinases: components of multiple signaling pathways

2000

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“…Similarly, PTPeC, has been shown to inhibit JAK kinase phosphorylation resulting in inhibition of dierentiation and apoptosis in M1 cells stimulated by IL-6 and LIF (Tanuma et al, 2000). Bittorf et al (1999) recently showed that SHP1 inhibited erythropoietin-induced erythroid dierentiation and inhibition of apoptosis in an erythroleukemic cell line. This eect of SHP1 was a result of inhibition of both the JAK kinase and MAP kinase pathways.…”

Section: Negative Regulation By Protein Tyrosine Phosphatases (Ptps)mentioning

confidence: 99%

JAKs, STATs and Src kinases in hematopoiesis

Rane¹,

2002

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Hematopoiesis is the cumulative result of intricately regulated signal transduction cascades that are mediated by cytokines and their cognate receptors. Proper culmination of these diverse signaling pathways forms the basis for an orderly generation of dierent cell types and aberrations in these pathways is an underlying cause for diseases such as leukemias and other myeloproliferative and lymphoproliferative disorders. Over the past decade, downstream signal transduction events initiated upon cytokine/growth factor stimulation have been a major focus of basic and applied biomedical research. As a result, several key concepts have emerged allowing a better understanding of the complex signaling processes. A group of transcription factors, termed signal transducers and activators of transcription (STATs) appear to orchestrate the downstream events propagated by cytokine/growth factor interactions with their cognate receptors. Similarly, cytoplasmic Janus protein tyrosine kinases (JAKs) and Src family of kinases seem to play a critical role in diverse signal transduction pathways that govern cellular survival, proliferation, dierentiation and apoptosis. Accumulating evidence suggests that STAT protein activation may be mediated by members of both JAK and Src family members following cytokine/growth factor stimulation. In addition, JAK kinases appear to be essential for the phosphorylation of the cytokine receptors which results in the creation of docking sites on the receptors for binding of SH2-containing proteins such as STATs, Src-kinases and other signaling intermediates. Cell and tissue-speci®city of cytokine action appears to be determined by the nature of signal transduction pathways activated by cytokine/receptor interactions. The integration of these diverse signaling cues from active JAK kinases, members of the Srcfamily kinases and STAT proteins, leads to cell proliferation, cell survival and dierentiation, the endpoint of the cytokine/growth factor stimulus.

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SHP1 Protein Tyrosine Phosphatase Negatively Modulates Erythroid Differentiation and Suppression of Apoptosis in J2E Erythroleukemic Cells

Cited by 36 publications

References 62 publications

Optimized orbitrap HCD for quantitative analysis of phosphopeptides

Optimized orbitrap HCD for quantitative analysis of phosphopeptides

Janus kinases: components of multiple signaling pathways

JAKs, STATs and Src kinases in hematopoiesis

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