2010
DOI: 10.1182/blood-2008-10-183558
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Induction of myeloproliferative disorder and myelofibrosis by thrombopoietin receptor W515 mutants is mediated by cytosolic tyrosine 112 of the receptor

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Cited by 70 publications
(61 citation statements)
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References 66 publications
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“…The ERK pathway is an important mediator of cell transformation by BCR-ABL and was recently suggested to play a role in myeloproliferative neoplasm downstream mutant thrombopoietin receptors. 36 Even though TEL-PDGFRb and KPb have been associated with different myeloproliferative neoplasms, we did not identify any difference in signaling by these two oncogenes.…”
Section: Discussioncontrasting
confidence: 63%
“…The ERK pathway is an important mediator of cell transformation by BCR-ABL and was recently suggested to play a role in myeloproliferative neoplasm downstream mutant thrombopoietin receptors. 36 Even though TEL-PDGFRb and KPb have been associated with different myeloproliferative neoplasms, we did not identify any difference in signaling by these two oncogenes.…”
Section: Discussioncontrasting
confidence: 63%
“…Previously, it was shown that this tyrosine also called 78 (intracellular tyrosine) is phosphorylated on the MPLW515A and that the double-mutant MPLW515A/Y591F induced a much more severe MPN in the mouse than the single MPLW515A mutant. 46 Furthermore, this tyrosine is also phosphorylated after TPO binding, and negatively regulates MPL signaling by promoting its internalization degradation as well as ERK signaling. [46][47][48] Asparagine is a polar residue in contrast to the negative charge represented by tyrosine phosphorylation and, thus, the Y591N mutation resembles a Y591 lossof-function, like Y591F, but possibly weaker because unlike phenylalanine, asparagine is polar.…”
Section: 41mentioning
confidence: 99%
“…46 Furthermore, this tyrosine is also phosphorylated after TPO binding, and negatively regulates MPL signaling by promoting its internalization degradation as well as ERK signaling. [46][47][48] Asparagine is a polar residue in contrast to the negative charge represented by tyrosine phosphorylation and, thus, the Y591N mutation resembles a Y591 lossof-function, like Y591F, but possibly weaker because unlike phenylalanine, asparagine is polar. When the Y591N mutant was expressed in Ba/F3 cells it induced a slight TPO hypersensitivity, which was associated with constitutive activation of STAT3 and ERK.…”
Section: 41mentioning
confidence: 99%
“…Sorted cells grown in the presence of growth factor and those selected for factor independence were then starved from serum and cytokines for 5 hours and lysed in 1% NP40 lysis buffer (containing 100 mM Na orthovanadate, 100 mM phenylmethylsulfonyl fluoride, and a cocktail of protease inhibitors), as described 42 and processed for Western blotting with antibodies against JAK2, STAT3, Erk1/2, or against phosphosites in these proteins that reflect activation. 43 The sources of antibodies were: anti-HA (Roche Diagnostics, Indianapolis, IN), anti-JAK2 (Santa Cruz, anti-actin, Sigma, St. Louis, MO), anti-phospho-JAK2 (Tyr1007/1008), anti-phospho-STAT1 (Tyr701), anti-phospho-STAT3 (Tyr705), anti-phospho-STAT5 (Tyr694), anti-phospho-extracellular signalregulated kinase 1/2 (Erk1/2; Tyr202/204), and antibodies recognizing Erk1/2 were obtained from Cell Signaling Technology Inc. (Danvers, MA).…”
Section: Xenotransplant Assaymentioning
confidence: 99%