ArticleMolecular and cellular biology1999
Role of phosphoinositide 3-kinase in activation of ras and mitogen-activated protein kinase by epidermal growth factor.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 280 citations in OpenAlex.
- PI3K Regulates Wild-type RAS Signaling to Confer Resistance to KRAS Inhibition.Cancer research · 2026Article
- Active R-RAS2/TC21 prevents cell cycle arrest and morphological alterations in mouse embryonic fibroblasts lacking RAS proteins.Oncogene · 2025Article
- Soft Corals-derived Dihydrosinularin Attenuates Neuronal Apoptosis in 6-hydroxydopamine-induced Cell Model of Parkinson's Disease by Regulating the PI3K Pathway.Current medicinal chemistry · 2025Article
- Kinase-independent synthesis of 3-phosphorylated phosphoinositides by a phosphotransferase.Nature cell biology · 2022Article
- Lacrimal gland budding requires PI3K-dependent suppression of EGF signaling.Science advances · 2021Article
- Protective effects of peptide FK18 against neuro-excitotoxicity in SH-SY5Y cells.Experimental and therapeutic medicine · 2021Article
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- PTPRS Regulates Colorectal Cancer RAS Pathway Activity by Inactivating Erk and Preventing Its Nuclear Translocation.Scientific reports · 2018Article
- Direct binding of MEK1 and MEK2 to AKT induces Foxo1 phosphorylation, cellular migration and metastasis.Scientific reports · 2017Article
- Non-canonical PI3K-Cdc42-Pak-Mek-Erk Signaling Promotes Immune-Complex-Induced Apoptosis in Human Neutrophils.Cell reports · 2016Article
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- DNA Damage Signalling and Repair Inhibitors: The Long-Sought-After Achilles' Heel of Cancer.Biomolecules · 2015Review
- Leptin induced GRP78 expression through the PI3K-mTOR pathway in neuronal cells.Scientific reports · 2014Article
- The activation of TLR7 regulates the expression of VEGF, TIMP1, MMP2, IL-6, and IL-15 in Hela cells.Molecular and cellular biochemistry · 2014Article
- Association between expression of X-linked inhibitor of apoptosis protein and the clinical outcome in a BRAF V600E-prevalent papillary thyroid cancer population.Thyroid : official journal of the American Thyroid Association · 2014Article
- Rapid induction of apoptosis by PI3K inhibitors is dependent upon their transient inhibition of RAS-ERK signaling.Cancer discovery · 2014Article
- Receptor tyrosine kinase (RTK) signalling in the control of neural stem and progenitor cell (NSPC) development.Molecular neurobiology · 2014Review
- Physiological epidermal growth factor concentrations activate high affinity receptors to elicit calcium oscillations.PloS one · 2014Article
- PLC-γ and PI3K link cytokines to ERK activation in hematopoietic cells with normal and oncogenic Kras.Science signaling · 2013Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The paradigm for activation of Ras and extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinase by extracellular stimuli via tyrosine kinases, Shc, Grb2, and Sos does not encompass an obvious role for phosphoinositide (PI) 3-kinase, and yet inhibitors of this lipid kinase family have been shown to block the ERK/MAP kinase signalling pathway under certain circumstances. Here we show that in COS cells activation of both endogenous ERK2 and Ras by low, but not high, concentrations of epidermal growth factor (EGF) is suppressed by PI 3-kinase inhibitors; since Ras activation is less susceptible than ERK2 activation, PI 3-kinase-sensitive events may occur both upstream of Ras and between Ras and ERK2. However, strong elevation of PI 3-kinase lipid product levels by expression of membrane-targeted p110alpha is by itself never sufficient to activate Ras or ERK2. PI 3-kinase inhibition does not affect EGF-induced receptor autophosphorylation or adapter protein phosphorylation or complex formation. The concentrations of EGF for which PI 3-kinase inhibitors block Ras activation induce formation of Shc-Grb2 complexes but not detectable EGF receptor phosphorylation and do not activate PI 3-kinase. The activation of Ras by low, but mitogenic, concentrations of EGF is therefore dependent on basal, rather than stimulated, PI 3-kinase activity; the inhibitory effects of LY294002 and wortmannin are due to their ability to reduce the activity of PI 3-kinase to below the level in a quiescent cell and reflect a permissive rather than an upstream regulatory role for PI 3-kinase in Ras activation in this system.
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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.