ArticleThe Journal of biological chemistry2011
Phosphoinositide 3-kinase regulates plasma membrane targeting of the Ras-specific exchange factor RasGRP1.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Phosphorylation of RasGRP1 by Shc3 prevents RasGRP1 degradation and contributes to Ras/c-Jun activation in hepatocellular carcinoma.Molecular and cellular biochemistry · 2024Article
- Exploring the multifaceted role of RASGRP1 in disease: immune, neural, metabolic, and oncogenic perspectives.Cell cycle (Georgetown, Tex.) · 2024Review
- A Focused Review of Ras Guanine Nucleotide-Releasing Protein 1 in Immune Cells and Cancer.International journal of molecular sciences · 2023Review
- Regulation of the Small GTPase Ras and Its Relevance to Human Disease.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Nurr1 performs its anti-inflammatory function by regulating RasGRP1 expression in neuro-inflammation.Scientific reports · 2020Article
- Importance of the REM (Ras exchange) domain for membrane interactions by RasGRP3.Biochimica et biophysica acta. Biomembranes · 2017Article
- A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.eLife · 2017Article
- Structural Basis for the Failure of the C1 Domain of Ras Guanine Nucleotide Releasing Protein 2 (RasGRP2) to Bind Phorbol Ester with High Affinity.The Journal of biological chemistry · 2016Article
- A Polybasic Plasma Membrane Binding Motif in the I-II Linker Stabilizes Voltage-gated CaV1.2 Calcium Channel Function.The Journal of biological chemistry · 2015Article
- Absence of both Sos-1 and Sos-2 in peripheral CD4(+) T cells leads to PI3K pathway activation and defects in migration.European journal of immunology · 2015Article
- Rapid induction of apoptosis by PI3K inhibitors is dependent upon their transient inhibition of RAS-ERK signaling.Cancer discovery · 2014Article
- RasGRP Ras guanine nucleotide exchange factors in cancer.Frontiers in biology · 2013Article
- Regulation of ras exchange factors and cellular localization of ras activation by lipid messengers in T cells.Frontiers in immunology · 2013Review
- Article
- RasGRP1, but not RasGRP3, is required for efficient thymic β-selection and ERK activation downstream of CXCR4.PloS one · 2013Article
- Regulation of RasGRP1 function in T cell development and activation by its unique tail domain.PloS one · 2012Article
- N-methyl-substituted fluorescent DAG-indololactone isomers exhibit dramatic differences in membrane interactions and biological activity.Chembiochem : a European journal of chemical biology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Receptor-induced targeting of exchange factors to specific cellular membranes is the predominant mechanism for initiating and compartmentalizing signal transduction by Ras GTPases. The exchange factor RasGRP1 has a C1 domain that binds the lipid diacylglycerol and thus can potentially mediate membrane localization in response to receptors that are coupled to diacylglycerol-generating phospholipase Cs. However, the C1 domain is insufficient for targeting RasGRP1 to the plasma membrane. We found that a basic/hydrophobic cluster of amino acids within the plasma membrane-targeting domain of RasGRP1 is instead responsible for plasma membrane targeting. This basic/hydrophobic cluster binds directly to phospholipid vesicles containing phosphoinositides via electrostatic interactions with polyanionic phosphoinositide headgroups and insertion of a tryptophan into the lipid bilayer. B cell antigen receptor ligation and other stimuli induce plasma membrane targeting of RasGRP1 by activating the phosphoinositide 3-kinase signaling pathway, which generates phosphoinositides within the plasma membrane. Direct detection of phosphoinositides by the basic/hydrophobic cluster of RasGRP1 provides a novel mechanism for coupling and co-compartmentalizing phosphoinositide 3-kinase and Ras signaling and, in coordination with diacylglycerol detection by the C1 domain, gives RasGRP1 the potential to serve as an integrator of converging signals from the phosphoinositide 3-kinase and phospholipase C pathways.
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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.