ArticleThe Biochemical journal2005
Activated STAT5 proteins induce activation of the PI 3-kinase/Akt and Ras/MAPK pathways via the Gab2 scaffolding adapter.
Article in The Biochemical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 114 citations in OpenAlex.
- IL-1β and associated molecules as prognostic biomarkers linked with immune cell infiltration in colorectal cancer: an integrated statistical and machine learning approach.Discover oncology · 2025Article
- Structural insights into Beclin 1 interactions with it's regulators for autophagy modulation.Computational and structural biotechnology journal · 2025Review
- Age-associated myeloid malignancies - the role of STAT3 and STAT5 in myelodysplastic syndrome and acute myeloid leukemia.FEBS letters · 2024Review
- GRB2 is a BECN1 interacting protein that regulates autophagy.Cell death & disease · 2024Article
- Antibody Deficiency in Patients with Biallelic KARS1 Mutations.Journal of clinical immunology · 2023Article
- The Impact of ETV6-NTRK3 Oncogenic Gene Fusions on Molecular and Signaling Pathway Alterations.Cancers · 2023Article
- Quantitative phosphoproteomic analysis reveals unique cAMP signaling pools emanating from AC2 and AC6 in human airway smooth muscle cells.Frontiers in physiology · 2023Article
- Loss of STAT5A promotes glucose metabolism and tumor growth through miRNA-23a-AKT signaling in hepatocellular carcinoma.Molecular oncology · 2021Article
- GRB2-associated binding protein 2 regulates multiple pathways associated with the development of prostate cancer.Oncology letters · 2020Article
- Regulation of the JAK2-STAT5 Pathway by Signaling Molecules in the Mammary Gland.Frontiers in cell and developmental biology · 2020Review
- Mechanism for IL-15-Driven B Cell Chronic Lymphocytic Leukemia Cycling: Roles for AKT and STAT5 in Modulating Cyclin D2 and DNA Damage Response Proteins.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Estrogen receptor-β of microglia underlies sexual differentiation of neuronal protection via ginsenosides in mice brain.CNS neuroscience & therapeutics · 2018Article
- Erythropoietin Rescues Memory Impairment in a Rat Model of Chronic Cerebral Hypoperfusion via the EPO-R/JAK2/STAT5/PI3K/Akt/GSK-3β Pathway.Molecular neurobiology · 2018Article
- Protective Roles of Interferon-γ in Cardiac Hypertrophy Induced by Sustained Pressure Overload.Journal of the American Heart Association · 2018Article
- Effects of Grb2-associated binding protein 2-specific siRNA on the migration and invasion of MG-63 osteosarcoma cells.Oncology letters · 2018Article
- Crosstalk between STAT5 activation and PI3K/AKT functions in normal and transformed mammary epithelial cells.Molecular and cellular endocrinology · 2017Review
- Review
- Intracellular Signaling Pathways Involved in Childhood Acute Lymphoblastic Leukemia; Molecular Targets.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2016Review
- Changes in Gab2 phosphorylation and interaction partners in response to interleukin (IL)-2 stimulation in T-lymphocytes.Scientific reports · 2016Article
- Grb2-associated binder-2 gene promotes migration of non-small cell lung cancer cells via Akt signaling pathway.American journal of translational research · 2016Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The active forms of STAT5A (signal transducer and activator of transcription 5A) and STAT5B are able to relieve the cytokine dependence of haematopoietic cells and to induce leukaemia in mice. We have demonstrated previously that activation of the PI3K (phosphoinositide 3-kinase) signalling cascade plays a major role in cell growth and survival induced by these proteins. Interaction between STAT5 and p85, the regulatory subunit of the PI3K, has been suggested to be required for this activation. We show in the present study that the scaffolding protein Gab2 [Grb2 (growth-factor-receptor-bound protein 2)-associated binder-2] is an essential component of this interaction. Gab2 is persistently tyrosine-phosphorylated in Ba/F3 cells expressing caSTAT5 (constitutively activated STAT5), independent of JAK2 (Janus kinase 2) activation where it interacts with STAT5, p85 and Grb2, but not with Shp2 [SH2 (Src homology 2)-domain-containing tyrosine phosphatase] proteins. Interaction of STAT5 with Gab2 was also observed in Ba/F3 cells stimulated with interleukin-3 or expressing the oncogenic fusion protein Tel-JAK2. The MAPKs (mitogen-activated protein kinases) ERK1 (extracellular-signal-regulated kinase 1) and ERK2 were constitutively activated in the caSTAT5-expressing cells and were found to be required for caSTAT5-induced cell proliferation. Overexpression of Gab2-3YF, a mutant of Gab2 incapable of binding PI3K, inhibited the proliferation and survival of caSTAT5-expressing cells as well as ERK1/2 and Akt/protein kinase B phosphorylation. Taken together, our results indicate that Gab2 is required for caSTAT5-induced cell proliferation by regulating both the PI3K/Akt and the Ras/MAPK pathways.
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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.