ArticleScience signaling2013
PLC-γ and PI3K link cytokines to ERK activation in hematopoietic cells with normal and oncogenic Kras.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Oncogenic stress response mechanisms as new therapeutic targets in cancer treatment: A review.Medicine · 2025Review
- Targeting neurotrophic dysregulation in diabetic retinopathy: a novel therapeutic avenue.Molecular biology reports · 2025Review
- Generating and validating renewable affimer protein binding reagents targeting SH2 domains.Scientific reports · 2024Article
- ERK1/2 in immune signalling.Biochemical Society transactions · 2022Review
- Novel therapeutic approaches for pancreatic cancer by combined targeting of RAF→MEK→ERK signaling and autophagy survival response.Annals of translational medicine · 2019Article
- Tonic ATP-mediated growth suppression in peripheral nerve glia requires arrestin-PP2 and is evaded in NF1.Acta neuropathologica communications · 2018Article
- Mechanistic and Preclinical Insights from Mouse Models of Hematologic Cancer Characterized by Hyperactive Ras.Cold Spring Harbor perspectives in medicine · 2018Review
- Survival of pancreatic cancer cells lacking KRAS function.Nature communications · 2017Article
- Stat5 is critical for the development and maintenance of myeloproliferative neoplasm initiated by Nf1 deficiency.Haematologica · 2016Article
- Article
- Ras-related C3 Botulinum Toxin Substrate (Rac) and Src Family Kinases (SFK) Are Proximal and Essential for Phosphatidylinositol 3-Kinase (PI3K) Activation in Natural Killer (NK) Cell-mediated Direct Cytotoxicity against Cryptococcus neoformans.The Journal of biological chemistry · 2016Article
- Urotensin-II receptor stimulation of cardiac L-type Ca2+ channels requires the βγ subunits of Gi/o-protein and phosphatidylinositol 3-kinase-dependent protein kinase C β1 isoform.The Journal of biological chemistry · 2015Article
- Article
- RasGRP Ras guanine nucleotide exchange factors in cancer.Frontiers in biology · 2013Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Oncogenic K-Ras proteins, such as K-Ras(G12D), accumulate in the active, guanosine triphosphate (GTP)-bound conformation and stimulate signaling through effector kinases. The presence of the K-Ras(G12D) oncoprotein at a similar abundance to that of endogenous wild-type K-Ras results in only minimal phosphorylation and activation of the canonical Raf-mitogen-activated or extracellular signal-regulated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling cascades in primary hematopoietic cells, and these pathways remain dependent on growth factors for efficient activation. We showed that phospholipase C-γ (PLC-γ), PI3K, and their generated second messengers link activated cytokine receptors to Ras and ERK signaling in differentiated bone marrow cells and in a cell population enriched for leukemia stem cells. Cells expressing endogenous oncogenic K-Ras(G12D) remained dependent on the second messenger diacylglycerol for the efficient activation of Ras-ERK signaling. These data raise the unexpected possibility of therapeutically targeting proteins that function upstream of oncogenic Ras in cancer.
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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.