ArticleBlood2007
SHP-2 phosphatase is required for hematopoietic cell transformation by Bcr-Abl.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 43 citations in OpenAlex.
- PTPN11 in cartilage development, adult homeostasis, and diseases.Bone research · 2025Review
- SHP2 inhibition displays efficacy as a monotherapy and in combination with JAK2 inhibition in preclinical models of myeloproliferative neoplasms.American journal of hematology · 2024Article
- Article
- Targeting the PTP1B-Bcr-Abl1 interaction for the degradation of T315I mutant Bcr-Abl1 in chronic myeloid leukemia.Cancer science · 2023Article
- Regulatory Molecules and Corresponding Processes of BCR-ABL Protein Degradation.Journal of Cancer · 2019Review
- SHP2 is required for BCR-ABL1-induced hematologic neoplasia.Leukemia · 2018Article
- A derivative of epigallocatechin-3-gallate induces apoptosis via SHP-1-mediated suppression of BCR-ABL and STAT3 signalling in chronic myelogenous leukaemia.British journal of pharmacology · 2015Article
- Tanshinone-1 induces tumor cell killing, enhanced by inhibition of secondary activation of signaling networks.Cell death & disease · 2013Article
- PECAM-1 is involved in BCR/ABL signaling and may downregulate imatinib-induced apoptosis of Philadelphia chromosome-positive leukemia cells.International journal of oncology · 2013Article
- Inhibition of protein-tyrosine phosphatase 1B (PTP1B) mediates ubiquitination and degradation of Bcr-Abl protein.The Journal of biological chemistry · 2011Article
- Global phosphoproteomics reveals crosstalk between Bcr-Abl and negative feedback mechanisms controlling Src signaling.Science signaling · 2011Article
- The protein tyrosine phosphatase SHP-2 is required for EGFRvIII oncogenic transformation in human glioblastoma cells.Experimental cell research · 2009Article
- Charting the molecular network of the drug target Bcr-Abl.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- SHP-2 tyrosine phosphatase in human diseases.International journal of clinical and experimental medicine · 2009Article
- SHP-2 is a novel target of Abl kinases during cell proliferation.Journal of cell science · 2008Article
- Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration.Molecular cancer therapeutics · 2008Article
- Subcellular distribution of p210(BCR-ABL) in CML cell lines and primary CD34+ CML cells.Leukemia · 2008Article
- The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury.Histology and histopathology · 2007Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
SHP-2 phosphatase forms a stable protein complex with and is heavily tyrosine-phosphorylated by the oncogenic tyrosine kinase Bcr-Abl. However, the role of SHP-2 in Bcr-Abl-mediated leukemogenesis is unclear. In the present report, we provide evidence that SHP-2 is required for hematopoietic cell transformation by Bcr-Abl. In vitro biological effects of Bcr-Abl transduction were diminished in SHP-2Delta/Delta hematopoietic cells, and the leukemic potential of Bcr-Abl-transduced SHP-2Delta/Delta cells in recipient animals was compromised. Further analyses showed that Bcr-Abl protein (p210) was degraded, and its oncogenic signaling was greatly decreased in SHP-2Delta/Delta cells. Treatment with proteasome inhibitors or reintroduction of SHP-2 restored p210 level in Bcr-Abl-transduced SHP-2Delta/Delta cells. Subsequent investigation revealed that SHP-2 interacted with heat shock protein 90, an important chaperone protein protecting p210 from proteasome-mediated degradation. The role of SHP-2 in the stability of p210 is independent of its catalytic activity. Blockade of SHP-2 expression in p210-expressing cells by antisense or small-interfering RNA approaches decreased p210 level, causing cell death. Inhibition of SHP-2 enzymatic activity by overexpression of catalytically inactive SHP-2 mutant did not destabilize p210 but enhanced serum starvation-induced apoptosis, suggesting that SHP-2 also plays an important role in downstream signaling of p210 kinase. These studies identified a novel function of SHP-2 and suggest that SHP-2 might be a useful target for controlling Bcr-Abl-positive leukemias.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.