Affinage

RASGRP1

RAS guanyl-releasing protein 1 · UniProt O95267

Length
797 aa
Mass
90.4 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RASGRP1 is a diacylglycerol (DAG)- and calcium-regulated guanine nucleotide exchange factor (GEF) that couples antigen-receptor and phospholipase-C signaling to Ras-ERK activation, and it is the essential, non-redundant link between TCR/DAG signaling and Ras during thymocyte maturation (PMID:9582122, PMID:11017103). Its activation is governed by membrane recruitment: a high-affinity C1 domain binds DAG/phorbol esters and drives translocation to membranes, while a Plasma membrane Targeter (PT) domain binds PI3K-generated phosphoinositides, and these inputs are countered by a Suppressor-of-PT domain and modulated by an EF-hand whose alternative splicing tunes targeting (PMID:9819387, PMID:10779365, PMID:17567957, PMID:21285350). In the resting state RASGRP1 is autoinhibited, with the Ras-binding site blocked by an interdomain linker and the membrane surface buried in a dimerization interface; calcium binding and a His212 pH-sensing fulcrum drive the conformational transition to the active form (PMID:23908768, PMID:28952923). Once membrane-localized, RASGRP1 catalyzes nucleotide exchange on Ras at both the plasma membrane and the Golgi—a Golgi compartment specificity unique to the RasGRP family—and amplifies signaling by generating RasGTP that primes the allosteric pocket of SOS, establishing a positive feedback loop that explains its dominance in lymphocytes (PMID:12845332, PMID:12782630, PMID:17283063). Activity is further tuned by PKC-dependent Thr184 phosphorylation, DGKalpha-mediated DAG clearance, and negative regulation by the adaptor SKAP55, and expression is controlled transcriptionally by RUNX1/CBFB and an hnRNP-K-bound enhancer and post-transcriptionally by SRSF1-dependent exon-11 splicing (PMID:11919165, PMID:15899849, PMID:18320039, PMID:29905030, PMID:31164884, PMID:33065764). Beyond canonical Ras signaling, RASGRP1 acts as a GEF for Rheb to activate mTOR in striatal neurons and interfaces with cytoskeletal dynamics via DYNLL1 (PMID:24336796, PMID:27776107, PMID:32426479). Human biallelic loss of RASGRP1 causes a combined immunodeficiency with impaired T/B cell ERK signaling and defective NK cytotoxicity (PMID:27776107).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1998 High

    Established RASGRP1 as a Ras GEF and identified DAG-driven membrane translocation through its C1 domain as the activation mechanism, defining the protein's core biochemical logic.

    Evidence NIH 3T3 transformation, subcellular fractionation, and domain-deletion/substitution mutagenesis with GEF and MAPK readouts

    PMID:9582122 PMID:9819387

    Open questions at the time
    • Did not resolve which Ras isoforms or compartments are engaged in physiological cells
    • Activation mechanism studied in fibroblasts, not lymphocytes
  2. 2000 High

    Demonstrated that RASGRP1 is the essential, non-redundant GEF linking TCR/PLC-gamma/DAG signaling to Ras and is required for mature thymocyte development, moving it from a transforming protein to a physiological immune signaling node.

    Evidence Antibody inhibition and overexpression in Jurkat cells plus a targeted knockout mouse with thymocyte phenotyping and Ras activation assays

    PMID:10807788 PMID:11017103

    Open questions at the time
    • Did not define the spatial site of Ras activation
    • Mechanism of how DAG signal is converted to sustained Ras output unresolved
  3. 2000 High

    Quantified the C1 domain as a high-affinity DAG/phorbol ester receptor distinct from PKC, establishing the ligand-binding basis of recruitment.

    Evidence Radioligand binding ([3H]PDBu) with competition and cofactor analysis

    PMID:10779365

    Open questions at the time
    • In vitro binding did not address membrane discrimination in cells
  4. 2003 High

    Revealed compartmentalized Ras signaling: RASGRP1 activates Ras at the Golgi, a localization unique to the RasGRP family, with calcium positively regulating Golgi Ras while distinct GAPs negatively regulate plasma membrane Ras.

    Evidence Live-cell imaging of GFP-tagged RasGRP1 and Ras biosensors with compartment-resolved activation assays in Jurkat cells; systematic GEF comparison

    PMID:12782630 PMID:12845332

    Open questions at the time
    • How C1 versus other domains select internal versus plasma membrane was not fully resolved
    • Functional consequence of Golgi versus PM Ras pools unclear
  5. 2005 High

    Defined a DAG-PKC-RasGRP1-Ras-ERK feedback circuit by identifying Thr184 phosphorylation by novel PKC as a positive regulatory event.

    Evidence RasGRP1-deficient Jurkat clones, RNAi, phospho-specific antibodies, and PKC inhibitors

    PMID:15899849

    Open questions at the time
    • Precise effect of Thr184 phosphorylation on conformation or localization not structurally defined
  6. 2007 High

    Showed RASGRP1 amplifies Ras signaling by priming the SOS allosteric pocket with RasGTP, explaining its dominance in initiating lymphocyte Ras-ERK feedback.

    Evidence Genetic knockout/reconstitution in Jurkat and DT40 cells with allosteric SOS mutants and RasV12C40 substitution

    PMID:17283063

    Open questions at the time
    • Quantitative kinetics of the RasGRP1-SOS handoff in vivo not established
  7. 2007 Medium

    Dissected the membrane-targeting machinery, defining cooperative C1, PT, and SuPT domains and the C-terminal tail as determinants of receptor-induced localization.

    Evidence Domain deletion/mutational analysis with live imaging in B cells and fibroblasts, and tail-deleted knock-in mice

    PMID:17567957 PMID:22719950

    Open questions at the time
    • Single-lab studies
    • Molecular partners mediating tail-dependent trafficking unidentified
  8. 2009 Medium

    Established that EF1, independent of bulk calcium flux, and its alternative splicing modulate plasma membrane targeting by counteracting the SuPT domain, with the GEF Ras-binding site itself feeding back into localization.

    Evidence EF-hand mutagenesis, splice isoform expression, calcium chelation, and live imaging in B cells

    PMID:19168098

    Open questions at the time
    • Single lab
    • Physiological splice ratios and their regulation not quantified here
  9. 2011 Medium

    Connected PI3K signaling to RASGRP1 recruitment by demonstrating direct phosphoinositide binding by a basic/hydrophobic cluster in the PT domain.

    Evidence Lipid vesicle binding assays, PI3K inhibitors, cluster mutagenesis, and BCR ligation imaging

    PMID:21285350

    Open questions at the time
    • Single lab
    • Relative contribution of PT/phosphoinositide versus C1/DAG in vivo not quantified
  10. 2011 High

    Identified a calcium-driven, DAG-independent RASGRP1/PKC-delta proapoptotic ERK pathway required for negative selection of autoreactive B cells, distinguishing it biochemically from canonical DAG-driven ERK.

    Evidence PKC-delta knockout mice, STIM1 and RasGRP1 manipulation, and pathway-resolved ERK and apoptosis assays

    PMID:21441934

    Open questions at the time
    • How calcium converts ERK output to proapoptotic rather than proliferative not fully mechanistic
  11. 2013 High

    Provided the structural basis for autoinhibition and calcium-dependent activation, showing the Ras-binding site is blocked and the membrane surface buried in a dimerization interface that calcium disrupts.

    Evidence X-ray crystallography, NMR, and structure-guided mutagenesis

    PMID:23908768

    Open questions at the time
    • Full-length protein with all regulatory domains not crystallized
    • Membrane-bound active conformation not directly visualized
  12. 2013 Medium

    Revealed an oncogenic mode in T-ALL where RASGRP1 overexpression raises basal Ras GTP-loading flux, enabling cytokine receptors to drive Ras independently of acute PLC-gamma/DAG.

    Evidence Multiple Ras-GTP flux assays and PLC-gamma inhibitor experiments in T-ALL versus normal thymocytes

    PMID:23532335

    Open questions at the time
    • Single lab
    • Mechanism enabling DAG-independent activation at baseline DAG unclear
  13. 2013 High

    Placed RASGRP1 upstream of mTOR in tonic T cell signaling using genetic epistasis, showing an EF-hand mutant uncouples reduced Ras-ERK from elevated mTOR-S6K activity and autoimmunity.

    Evidence ENU-derived Rasgrp1(Anaef) knock-in crossed to an Mtor reduction-of-function allele with S6K and T cell subset readouts

    PMID:24336796

    Open questions at the time
    • Direct biochemical link from RASGRP1 to mTOR not defined in this study
  14. 2015 High

    Defined a context-dependent negative-feedback role: in epithelial/colorectal cancer cells RASGRP1 opposes EGFR-SOS1-Ras signaling, contrasting with its amplifying role in lymphocytes.

    Evidence Rasgrp1 conditional knockout in KrasG12D and Apc-mutant mice with EGFR stimulation and organoid proliferation assays

    PMID:26005835

    Open questions at the time
    • Molecular basis of the RASGRP1-SOS1 opposition not structurally resolved
  15. 2015 Medium

    Showed that net oncogenic Ras output in RASGRP1-overexpressing T-ALL is set by the balance between RASGRP1-driven GTP loading and RasGAP-driven hydrolysis, with cytokines acting by decreasing GAP activity.

    Evidence Ras-GTP pull-down, exchange-rate assays, and Akt/ERK readouts with PLC-gamma controls

    PMID:26549032

    Open questions at the time
    • Single lab
    • Identity of the cytokine-regulated GAP not defined
  16. 2016 High

    Identified human RASGRP1 loss-of-function as a cause of combined immunodeficiency and linked RASGRP1 to cytoskeletal/NK cell function via RhoA activation and a DYNLL1 interaction.

    Evidence Homozygosity mapping, exome sequencing, WT rescue, interaction proteomics, and RhoA/NK cytotoxicity assays

    PMID:27776107

    Open questions at the time
    • How RASGRP1 controls RhoA and DYNLL1-dependent cytoskeletal events mechanistically unresolved
  17. 2016 Medium

    Showed RASGRP1 stabilizes the striatal GTPase Rhes and shapes its interactome, extending RASGRP1 function into neuronal/behavioral regulation.

    Evidence Rhes-heterozygous and RasGRP1 knockout mice, striatal Rhes-interactome proteomics, and locomotor behavioral assays

    PMID:27902448

    Open questions at the time
    • Single lab
    • Whether stabilization reflects direct GEF/binding activity not resolved
  18. 2017 High

    Defined His212 as a pH-sensing fulcrum controlling the autoinhibited-to-active transition, with SNP variants altering signaling and membrane recruitment.

    Evidence Crystal structure comparison, NMR of pH-dependent changes, and functional assays of His212 variants

    PMID:28952923

    Open questions at the time
    • Physiological contexts where intracellular pH gates RASGRP1 not established
  19. 2018 Medium

    Established post-transcriptional control of RASGRP1 by SRSF1, which binds exon 11 and promotes its inclusion to maintain wild-type protein, relevant to lupus T cell dysfunction.

    Evidence Oligonucleotide-protein pulldown, SRSF1 loss/gain of function, splicing RT-PCR, and Western blot in healthy and SLE T cells

    PMID:29905030

    Open questions at the time
    • Single lab
    • Functional difference between exon-11-included and -skipped isoforms not biochemically defined
  20. 2019 Medium

    Identified an intronic enhancer SNP whose risk allele binds hnRNP-K to drive T-cell-specific RASGRP1 transcription, linking genetic variation to ERK/MAPK signaling.

    Evidence Allele-specific luciferase, EMSA, mass spectrometry, ChIP-qPCR, and hnRNP-K inhibition with functional readouts

    PMID:31164884

    Open questions at the time
    • Single lab
    • In vivo contribution of the enhancer to autoimmunity not tested
  21. 2020 Medium

    Defined RUNX1/CBFB transcriptional activation of RASGRP1 via an intrinsic enhancer, connecting reduced RUNX1 to lowered RASGRP1 in autoimmune T cells.

    Evidence CRISPR-Cas9 enhancer disruption, H3K27ac ChIP-seq, RUNX1/CBFB binding confirmation, and expression/ERK assays

    PMID:33065764

    Open questions at the time
    • Single lab
    • Interplay with the hnRNP-K enhancer not integrated
  22. 2020 Medium

    Demonstrated a non-Ras catalytic function: RASGRP1 acts as a Rheb GEF to drive ERK/mTOR-dependent L-DOPA-induced dyskinesia in the striatum.

    Evidence RasGRP1 knockout in a parkinsonian model with dyskinesia behavior, striatal ERK/mTOR phosphorylation, and proteomics

    PMID:32426479

    Open questions at the time
    • Direct reconstitution of Rheb GEF activity not performed
    • Single lab
  23. 2010 Medium

    Extended RASGRP1 signaling to renal epithelium, where it drives Ras-ERK-dependent ubiquitination and dynamin-dependent endocytosis of the NCC cotransporter.

    Evidence RasGRP1 siRNA, surface NCC biotinylation, internalization and ubiquitin assays, and dominant-negative dynamin in distal convoluted tubule cells

    PMID:18077438 PMID:20392800

    Open questions at the time
    • Single lab
    • Physiological trigger of RASGRP1 in renal tubule in vivo unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory inputs (C1/DAG, PT/phosphoinositide, EF-hand/calcium, His212/pH, Thr184 phosphorylation) are integrated on a full-length, membrane-bound RASGRP1 to set compartment-specific Ras versus Rheb output remains unresolved.
  • No full-length membrane-bound active structure
  • Quantitative integration of the regulatory inputs not modeled
  • Direct biochemical demonstration of Rheb GEF activity outstanding

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005794 Golgi apparatus 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
DYNLL1GNAI2HSP90RHESSKAP55SOS1ZAP-70

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 RasGRP1 is a guanine nucleotide exchange factor (GEF) for Ras that contains a DAG-binding C1 domain and calcium-binding EF-hand motifs. DAG analog treatment caused sustained Ras-ERK activation and membrane partitioning of RasGRP1; deletion of the DAG-binding domain abolished both membrane recruitment and sustained signaling, establishing that DAG-driven membrane translocation is the primary activation mechanism. Cell transformation assays in NIH 3T3 fibroblasts, subcellular fractionation, domain deletion mutagenesis, Ras-GTP assays Science High 9582122
1998 The C1 domain of RasGRP1 is required for transforming activity; deletion of the C1 domain or an adjacent basic-amino-acid cluster abolished transformation and MAP kinase activation. Replacement of the C1 domain with a membrane-targeting prenylation signal or a PKC C1 domain restored activity, confirming that membrane recruitment via the C1 domain is the mechanistic basis of RasGRP1 activation. Phorbol ester stimulates C1-domain-dependent translocation of RasGRP1 to cell membranes. NIH 3T3 transformation assay, C1-domain deletion and substitution mutagenesis, MAP kinase activation assay, confocal microscopy of GFP-tagged protein Molecular and cellular biology High 9819387
2000 RasGRP1 is required for TCR-induced Ras activation in T cells. A PLC-γ1 inhibitor reduced TCR-stimulated Ras activation; anti-RasGRP1 antibodies inhibited Ras-guanyl nucleotide exchange activity in TCR-stimulated Jurkat cell membranes. Overexpression of RasGRP1 enhanced TCR-Ras-ERK signaling and IL-2 secretion in response to DAG analogues plus calcium ionophore, directly linking PLC-γ1/DAG to Ras through RasGRP1. Ras-GTP pull-down assay, antibody inhibition of GEF activity in membrane fractions, RasGRP1 overexpression in Jurkat T cells, ERK activation assay, IL-2 ELISA Blood High 10807788
2000 RasGRP1 (RasGRP) knockout mice show normal numbers of immature thymocytes but a marked deficiency of mature single-positive (CD4+ and CD8+) thymocytes. Mutant thymocytes completely lack Ras signaling and proliferative responses to DAG analogs or TCR stimulation, establishing RasGRP1 as an essential and non-redundant link between TCR/DAG signaling and Ras activation in thymic development. Targeted gene knockout in mice, thymocyte FACS phenotyping, Ras activation assay, thymocyte proliferation assay Nature immunology High 11017103
2000 The C1 domain of RasGRP1 binds phorbol esters with high affinity (Kd ~0.58 nM for [3H]PDBu), comparable to PKC. Lipid cofactor requirements differ from PKC; calcium does not affect phorbol ester binding to the C1-EF domain, establishing the C1 domain as the primary high-affinity DAG/phorbol ester receptor on RasGRP1. Radioligand binding assay ([3H]PDBu), competition binding with DAG analogs and PKC inhibitors, phospholipid cofactor requirement analysis Molecular pharmacology High 10779365
2002 Expression of a catalytically inactive diacylglycerol kinase alpha (DGKα) in T cells leads to sustained membrane translocation of RasGRP1 and sustained MAPK activation following TCR or muscarinic receptor stimulation, demonstrating that DGKα-mediated DAG clearance controls the duration of RasGRP1 activation and downstream Ras/MAPK signaling. Expression of kinase-dead DGKα in T cell lines, time-course imaging of RasGRP1 translocation, MAPK activation assay, DAG measurement FASEB journal Medium 11919165
2003 In response to Src-dependent activation of PLCγ1, RasGRP1 translocates to the Golgi apparatus where it activates Ras. Calcium positively regulates Golgi Ras through RasGRP1, while the same messenger negatively regulates plasma membrane Ras via the GAP CAPRI, demonstrating compartmentalized Ras signaling through distinct regulatory mechanisms. Live-cell imaging of GFP-tagged RasGRP1 and Ras biosensors, dominant-negative and constitutively active construct expression, Ras activation assays in Jurkat T cells Nature High 12845332
2003 RasGRP family members are the only Ras activators that localize to and activate Ras at the Golgi. Ras activation at the plasma membrane and ER can be achieved by most GEFs, but GTP loading of Ras at the Golgi is specific to RasGRP proteins, establishing a basis for compartmentalized Ras signaling. Subcellular fractionation, confocal microscopy of GFP-tagged GEFs, Ras activation assays in different membrane compartments The Journal of biological chemistry High 12782630
2004 The C1 domains of RasGRP1 and PKCθ show distinct subcellular localization in living T lymphocytes despite high structural similarity, with RasGRP1 C1 domain preferentially accumulating at internal membranes (Golgi) following TCR triggering, while PKCθ C1 domain targets the plasma membrane. Overexpression of individual C1 domains can attenuate DAG-dependent signals from respective membranes, establishing these domains as functional DAG discriminators. Live-cell imaging with fluorescent C1 domain fusion proteins, pharmacological stimulation and TCR triggering, Ras activation reporter assays in Jurkat T cells Molecular biology of the cell Medium 15064353
2005 RasGRP1 is required for optimal antigen receptor-triggered Ras-ERK activation in T cells, and relies on its DAG-binding domain for selective Erk kinase activation. Phosphorylation of threonine 184 (Thr184) in RasGRP1 correlates with ERK activation and requires novel PKC kinase activities. PKCθ activation is in turn dependent on RasGRP1, establishing a DAG-PKC-RasGRP1-Ras-ERK pathway with positive feedback. RasGRP1-deficient Jurkat T cell clones, RNAi knockdown, phospho-specific antibodies, domain deletion constructs, PKC pharmacological inhibitors Molecular and cellular biology High 15899849
2007 RasGRP1 orchestrates Ras signaling in two ways: (i) by directly activating Ras and (ii) by generating RasGTP that primes the allosteric pocket of SOS, enhancing SOS activity and creating a positive RasGTP-SOS feedback loop. Without RasGRP1, this loop cannot be initiated because SOS requires its own product (RasGTP) for allosteric activation, explaining RasGRP1 dominance in lymphocytes. Jurkat and DT40 B cell genetic knockouts and reconstitution, allosteric SOS mutants, RasV12C40 expression to substitute RasGRP function, Ras-GTP quantification Molecular and cellular biology High 17283063
2007 RasGRP1 is required for membrane translocation and activation; the tail domain (C-terminal ~200 residues) is essential for membrane trafficking of RasGRP1 following TCR stimulation, and its deletion abolishes ERK activation despite intact C1 and EF domains. Knock-in mice expressing tail-deleted RasGRP1, TCR stimulation assays, subcellular fractionation, ERK phosphorylation assay, FACS analysis PloS one Medium 22719950
2007 The adaptor protein SKAP-55 binds RasGRP1 via its C-terminus in a manner enhanced by SKAP-55 tyrosine phosphorylation. This interaction negatively regulates the Ras-ERK pathway: SKAP-55 deficiency leads to increased RasGRP1 localization at the trans-Golgi network and hyper-activation of ERK following TCR stimulation. Co-immunoprecipitation, RNAi knockdown, SKAP-55 knockout T cells, confocal microscopy of RasGRP1 localization, ERK phosphorylation assay PloS one Medium 18320039
2007 BCR-induced plasma membrane targeting of RasGRP1 requires cooperativity between three domains: the C1 domain (binds DAG generated by PLCγ2), the Plasma membrane Targeter (PT) domain (sufficient and essential for plasma membrane targeting), and the Suppressor of PT (SuPT) domain (attenuates constitutive PM localization). In fibroblasts, the PT domain is inactive, so the C1 domain directs RasGRP1 to internal membranes. Domain deletion and mutational analysis, live fluorescence imaging in B cell lines and fibroblasts, BCR ligation experiments Molecular biology of the cell Medium 17567957
2009 One EF-hand (EF1) of RasGRP1 is required for receptor-induced translocation to the plasma membrane in B cells by counteracting the SuPT domain, independently of antigen receptor-induced calcium flux. Alternative splicing of EF1 modulates RasGRP1 plasma membrane targeting. The GEF domain Ras-binding site is required for both PT- and C1-mediated membrane localizations, suggesting positive feedback from Ras engagement. EF-hand mutagenesis, alternative splice isoform expression, calcium chelator experiments, live-cell fluorescence imaging in B cell lines Biochimica et biophysica acta Medium 19168098
2011 Phosphoinositide 3-kinase (PI3K) signaling controls plasma membrane targeting of RasGRP1. A basic/hydrophobic cluster within the PT domain of RasGRP1 binds directly to phosphoinositide-containing lipid vesicles via electrostatic interactions, and BCR ligation-induced PI3K activity generates plasma membrane phosphoinositides that recruit RasGRP1. Lipid vesicle binding assays, PI3K inhibitors, mutagenesis of basic/hydrophobic cluster, BCR ligation experiments, fluorescence imaging The Journal of biological chemistry Medium 21285350
2011 SDF-1 (CXCL12) stimulation via CXCR4 causes RasGRP1 to localize to the plasma membrane (activating K-Ras) and to the Golgi (activating N-Ras) through a novel signaling complex containing RasGRP1, Gαi2, and ZAP-70. This translocation does not require the DAG-binding domain for localization but does require it for activity. CXCR4-mediated RasGRP1 mobilization also requires TCR expression. RasGRP1 RNAi knockdown in human T cells, co-immunoprecipitation of RasGRP1/Gαi2/ZAP-70 complex, confocal microscopy of RasGRP1 localization, Ras isoform activation assays (K-Ras vs N-Ras), migration assays Journal of immunology Medium 21856938
2011 PKC-δ and RasGRP1 together mediate a Ca2+-driven pathway for proapoptotic ERK activation in B cells that is biochemically distinct from DAG-driven ERK activation. This pathway depends on STIM1 concentration (which controls Ca2+ entry) and is required for negative selection of autoreactive B cells. PKC-δ knockout mice, RasGRP1 and STIM1 knockdown/overexpression, ERK phosphorylation assays distinguishing Ca2+- vs DAG-driven activation, B cell apoptosis assays Nature immunology High 21441934
2013 Crystal structure of a RasGRP1 fragment reveals an autoinhibited conformation in which the Ras-binding site is blocked by an interdomain linker and the membrane-interaction surface is buried in a dimerization interface stabilized by the C-terminal oligomerization domain. NMR shows that calcium binding to the regulatory module induces conformational changes incompatible with the inactive assembly, providing the structural basis for calcium-dependent activation. X-ray crystallography, NMR spectroscopy, structure-guided mutagenesis eLife High 23908768
2013 RasGRP1 overexpression in T-ALL activates Ras downstream of cytokine receptors (IL-2, IL-7, IL-9) through a mechanism that does not require acute PLCγ-dependent DAG generation but relies on baseline DAG levels. Overexpression of RasGRP1 constitutively increases the GTP-loading rate of Ras, establishing a high flux through the RasGTP/GDP cycle that is counterbalanced by RasGAP activity. Ras-GTP pull-down assays, multiple RasGTP/GDP flux assays, PLCγ inhibitor experiments, cytokine stimulation in T-ALL vs normal thymocytes Science signaling Medium 23532335
2013 RasGRP1 missense mutation in the EF-hand (Anaef allele) reduces Ras-ERK activation but causes elevated tonic mTOR-S6K signaling and CD44 overexpression on naïve T cells. The mTOR-dependent T cell dysregulation and autoantibody production in Rasgrp1Anaef mice are rescued by a reduction-of-function Mtor mutation, placing RasGRP1 upstream of mTOR in tonic T cell signaling. ENU mutagenesis, Rasgrp1Anaef knock-in mice, Rasgrp1Anaef x Mtorchino double-mutant mice, S6K phosphorylation assays, T cell subset analysis eLife High 24336796
2015 RasGRP1 creates a negative feedback loop that limits proliferative EGFR-SOS1-Ras signals in colorectal cancer cells. RasGRP1 and SOS1 act in functional opposition downstream of EGFR; genetic Rasgrp1 depletion in mice with activating KRas mutation or Apc mutation exacerbates Ras-ERK signaling and cell proliferation. Rasgrp1 conditional knockout in KrasG12D and Apc-mutant mice, EGFR stimulation assays, ERK phosphorylation, intestinal organoid proliferation assays Nature cell biology High 26005835
2015 RasGRP1 overexpression in T-ALL increases basal Ras GTP-loading flux and enables IL-2/7/9 cytokine receptor signals to activate the Ras-Akt pathway. In these leukemic cells, cytokine stimulation decreases RasGAP activity rather than increasing GEF activity, revealing that the balance between RasGRP1-driven GTP loading and RasGAP-driven hydrolysis determines net oncogenic Ras signaling. Ras-GTP pull-down, nucleotide exchange rate assays, Akt/ERK phosphorylation assays, cytokine stimulation with PLCγ inhibitor controls Oncogene Medium 26549032
2016 RASGRP1 deficiency in humans causes combined immunodeficiency with impaired ERK phosphorylation in T and B cells, defective NK cell cytotoxicity with impaired granule convergence and actin accumulation, and decreased RhoA GTPase activation. Interaction proteomics identified DYNLL1 (dynein light chain) as a RasGRP1-interacting protein, linking RasGRP1 to cytoskeletal dynamics. Homozygosity mapping, exome sequencing, wild-type RASGRP1 rescue, interaction proteomics (Co-IP/MS), ERK phosphorylation assays, RhoA activation assay, NK cytotoxicity assay Nature immunology High 27776107
2016 RasGRP1 is an HSP90 client protein. HDAC inhibitor-induced HSP90 acetylation causes release and proteasomal degradation of RasGRP1 (and CRAF), leading to MAPK pathway downregulation and BIM upregulation in lymphoma cells. RasGRP1 siRNA mimics the pro-apoptotic effects of HDAC inhibitors. Co-immunoprecipitation of HSP90-RasGRP1 complex, HDAC inhibitor treatment, siRNA knockdown of RasGRP1, Western blotting for protein stability, BIM/apoptosis assays in vivo and in vitro Leukemia Medium 27890930
2017 His212 in RasGRP1 functions as a pH sensor that alters the balance between inactive and active conformations. Structural comparison of autoinhibited RasGRP1 and active RasGRP4:H-Ras/RasGRP2:Rap1b complexes shows that the transition involves rearrangement of an interdomain linker at a fulcrum where His212 is located. Charge alteration at His212 via SNP variants alters signaling activity and plasma membrane recruitment. Crystal structure comparison, NMR analysis of pH-dependent conformational changes, functional assays of His212 SNP variants (plasma membrane recruitment, Ras signaling) eLife High 28952923
2018 SRSF1 (serine/arginine-rich splicing factor 1) directly binds exon 11 of RASGRP1 pre-mRNA and promotes inclusion of exon 11, maintaining wild-type RASGRP1 protein expression. Silencing SRSF1 in healthy T cells increases the ratio of alternatively spliced (exon-11-skipped) to wild-type RASGRP1 and decreases RASGRP1 protein; conversely, overexpression of SRSF1 in SLE T cells restores RASGRP1 protein and downstream DNMT1/IL-2 expression. Oligonucleotide-protein pulldown assay (direct binding), SRSF1 siRNA and overexpression, RT-PCR splicing analysis, Western blotting Arthritis & rheumatology Medium 29905030
2019 An intronic enhancer in RASGRP1 (containing SNP rs11631591) drives cell-type-specific RASGRP1 transcription in T lymphocytes. The risk allele of rs11631591 binds hnRNP-K, and inhibition of hnRNP-K in Jurkat and primary T cells downregulates RASGRP1 and ERK/MAPK signaling. Luciferase reporter assay (allele-specific enhancer activity), EMSA, mass spectrometry identification of hnRNP-K, ChIP-qPCR, hnRNP-K inhibition with functional readout Frontiers in immunology Medium 31164884
2020 RUNX1 and its cofactor CBFB bind a RASGRP1 intrinsic enhancer and transcriptionally activate RASGRP1 expression. CRISPR-Cas9 disruption of this enhancer reduces RasGRP1 protein levels, and reduced RUNX1 expression in autoimmune patient CD4+ T cells correlates with decreased RASGRP1 levels. CRISPR-Cas9 enhancer disruption, ChIP-seq H3K27ac profiling, RUNX1/CBFB binding confirmation, RASGRP1 expression and ERK signaling assays European journal of immunology Medium 33065764
2020 RasGRP1 promotes L-DOPA-induced dyskinesia (LID) in the striatum by activating ERK and mTOR signaling. RasGRP1 acts as a GEF for Rheb (the activator of mTOR kinase complex) in addition to its canonical Ras GEF activity. RasGRP1 knockout mice show dramatically reduced LID without impaired L-DOPA therapeutic effects. RasGRP1 knockout mice in parkinsonian model, L-DOPA dyskinesia behavioral assays, ERK and mTOR phosphorylation in striatum, tandem mass spectrometry proteomics for downstream targets Science advances Medium 32426479
2010 Phorbol ester stimulation of RasGRP1 in renal distal convoluted tubule cells activates the Ras-ERK pathway and suppresses the surface expression and function of the sodium-chloride cotransporter (NCC) via NCC ubiquitination and dynamin-dependent endocytosis. RasGRP1 gene silencing prevents phorbol ester-induced Ras activation, ERK activation, NCC ubiquitination, and endocytosis. RasGRP1 siRNA knockdown, biotinylation assay of surface NCC, internalization assay, dynamin dominant-negative construct, ubiquitin immunoprecipitation, radiotracer NCC activity assay American journal of physiology. Renal physiology Medium 20392800
2007 Phorbol ester activates RasGRP1 in renal distal convoluted tubule cells, which in turn activates H-Ras and ERK1/2 MAPK in a PKC-independent manner, leading to suppression of NCC function and surface expression. RasGRP1 gene silencing prevents all of these effects, identifying RasGRP1 as the critical mediator of phorbol ester action on NCC. RasGRP1 siRNA knockdown, PKC/MAPK inhibitor experiments, 22Na+ radiotracer NCC activity assay, biotinylation of surface NCC, H-Ras activation assay Proceedings of the National Academy of Sciences Medium 18077438
2016 RasGRP1 interacts with and stabilizes Rhes (Ras homolog enriched in striatum), increasing Rhes synaptic accumulation in the striatum. RasGRP1 affects the composition of the amphetamine-induced Rhes interactome (Rhesactome), including proteins associated with neuropsychiatric disorders. Partial depletion of RasGRP1 attenuates the enhanced locomotor response to amphetamine seen in Rhes-heterozygous mice. Rhes-heterozygous and RasGRP1 knockout mouse models, proteomic analysis of striatal Rhes-interactome, locomotor behavioral assays, western blot for Rhes synaptic localization Science signaling Medium 27902448
2009 In B cells, RasGRP1 activates a proapoptotic pathway involving PKC/Ras-Raf-MEK-ERK signaling leading to phosphorylation of the BH3-only protein Bim by ERK on sites associated with increased apoptotic activity, followed by Bak-Bax complex formation and mitochondrial membrane permeabilization. This apoptosis can be suppressed by Bim downregulation or Bcl-2 overexpression. DAG analogue stimulation, in vitro ERK-Bim kinase assay, Bim siRNA, Bcl-2 overexpression, Bak-Bax co-immunoprecipitation, mitochondrial membrane potential assay Experimental hematology Medium 19100522
2004 SKAP55 co-immunoprecipitates with RasGRP1 via its C-terminus; this interaction is enhanced by tyrosine phosphorylation of SKAP55. Overexpression of SKAP55 disrupts TCR-to-Ras-ERK signaling, and this effect requires the RasGRP1-binding C-terminus of SKAP55; constitutively active Ras or Raf-1 overcome SKAP55 overexpression, placing the SKAP55-RasGRP1 interaction upstream of Ras. Co-immunoprecipitation, SKAP55 domain deletion constructs, TCR-induced ERK and AP-1 reporter assays, constitutively active Ras/Raf rescue Molecular immunology Low 17658605

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs. Science (New York, N.Y.) 565 9582122
2003 Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1. Nature 355 12845332
2000 RasGRP is essential for mouse thymocyte differentiation and TCR signaling. Nature immunology 350 11017103
2000 RasGRP links T-cell receptor signaling to Ras. Blood 287 10807788
1998 Regulation of RasGRP via a phorbol ester-responsive C1 domain. Molecular and cellular biology 195 9819387
2005 A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells. Molecular and cellular biology 164 15899849
2007 Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes. Molecular and cellular biology 145 17283063
2002 RasGRP1 transduces low-grade TCR signals which are critical for T cell development, homeostasis, and differentiation. Immunity 129 12433368
2004 Diacylglycerol-dependent binding recruits PKCtheta and RasGRP1 C1 domains to specific subcellular localizations in living T lymphocytes. Molecular biology of the cell 117 15064353
2005 RasGRP1 and RasGRP3 regulate B cell proliferation by facilitating B cell receptor-Ras signaling. Journal of immunology (Baltimore, Md. : 1950) 112 16301621
2016 RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics. Nature immunology 110 27776107
2003 Exchange factors of the RasGRP family mediate Ras activation in the Golgi. The Journal of biological chemistry 110 12782630
2000 The guanine nucleotide exchange factor RasGRP is a high -affinity target for diacylglycerol and phorbol esters. Molecular pharmacology 102 10779365
2011 STIM1, PKC-δ and RasGRP set a threshold for proapoptotic Erk signaling during B cell development. Nature immunology 101 21441934
2011 Regulation and Function of the RasGRP Family of Ras Activators in Blood Cells. Genes & cancer 94 21779502
2004 Vav1 transduces T cell receptor signals to the activation of the Ras/ERK pathway via LAT, Sos, and RasGRP1. The Journal of biological chemistry 80 14764585
2002 Expression of a catalytically inactive form of diacylglycerol kinase alpha induces sustained signaling through RasGRP. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 65 11919165
2013 Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1. eLife 64 23908768
2018 Loss of RASGRP1 in humans impairs T-cell expansion leading to Epstein-Barr virus susceptibility. EMBO molecular medicine 63 29282224
2015 RasGRP1 opposes proliferative EGFR-SOS1-Ras signals and restricts intestinal epithelial cell growth. Nature cell biology 62 26005835
2006 An essential role for RasGRP1 in mast cell function and IgE-mediated allergic response. The Journal of experimental medicine 55 17190838
2003 Autoimmunity as the consequence of a spontaneous mutation in Rasgrp1. Immunity 51 12932358
2009 Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side-effects induced by anti-parkinsonian therapy. Proceedings of the National Academy of Sciences of the United States of America 49 19171906
2005 A novel diacylglycerol-lactone shows marked selectivity in vitro among C1 domains of protein kinase C (PKC) isoforms alpha and delta as well as selectivity for RasGRP compared with PKCalpha. The Journal of biological chemistry 48 15923197
2017 RASGRP1 mutation in autoimmune lymphoproliferative syndrome-like disease. The Journal of allergy and clinical immunology 46 29155103
2013 RasGRP Ras guanine nucleotide exchange factors in cancer. Frontiers in biology 46 24744772
2017 Combined immunodeficiency with EBV positive B cell lymphoma and epidermodysplasia verruciformis due to a novel homozygous mutation in RASGRP1. Clinical immunology (Orlando, Fla.) 45 28822832
2013 Dysregulated RasGRP1 responds to cytokine receptor input in T cell leukemogenesis. Science signaling 45 23532335
2013 Rasgrp1 mutation increases naive T-cell CD44 expression and drives mTOR-dependent accumulation of Helios⁺ T cells and autoantibodies. eLife 44 24336796
2018 Novel Mutations in RASGRP1 are Associated with Immunodeficiency, Immune Dysregulation, and EBV-Induced Lymphoma. Journal of clinical immunology 43 30030704
2011 Critical roles of RasGRP1 for invariant NKT cell development. Journal of immunology (Baltimore, Md. : 1950) 43 21957144
2010 The transcription factor Gfi1 regulates G-CSF signaling and neutrophil development through the Ras activator RasGRP1. Blood 43 20203268
2010 RasGRP1 stimulation enhances ubiquitination and endocytosis of the sodium-chloride cotransporter. American journal of physiology. Renal physiology 41 20392800
2008 Preferential development of CD4 and CD8 T regulatory cells in RasGRP1-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 40 18424717
2015 RasGRP1 overexpression in T-ALL increases basal nucleotide exchange on Ras rendering the Ras/PI3K/Akt pathway responsive to protumorigenic cytokines. Oncogene 39 26549032
2009 Association of RASGRP1 with type 1 diabetes is revealed by combined follow-up of two genome-wide studies. Journal of medical genetics 39 19465406
2017 A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1. eLife 38 28952923
2003 RasGRP1 represents a novel non-protein kinase C phorbol ester signaling pathway in mouse epidermal keratinocytes. The Journal of biological chemistry 38 14532295
2009 A proapoptotic signaling pathway involving RasGRP, Erk, and Bim in B cells. Experimental hematology 36 19100522
2003 Diacylglycerols containing Omega 3 and Omega 6 fatty acids bind to RasGRP and modulate MAP kinase activation. The Journal of biological chemistry 36 14583629
2007 Phorbol ester stimulation of RasGRP1 regulates the sodium-chloride cotransporter by a PKC-independent pathway. Proceedings of the National Academy of Sciences of the United States of America 35 18077438
2009 RasGRP1 is required for human NK cell function. Journal of immunology (Baltimore, Md. : 1950) 34 19933860
2007 Transgenic overexpression of RasGRP1 in mouse epidermis results in spontaneous tumors of the skin. Cancer research 34 17210708
2005 Deregulated expression of RasGRP1 initiates thymic lymphomagenesis independently of T-cell receptors. Oncogene 33 15829980
2020 Nurr1 performs its anti-inflammatory function by regulating RasGRP1 expression in neuro-inflammation. Scientific reports 32 32612143
2011 A RasGRP, C. elegans RGEF-1b, couples external stimuli to behavior by activating LET-60 (Ras) in sensory neurons. Neuron 32 21482356
2001 Iridals are a novel class of ligands for phorbol ester receptors with modest selectivity for the RasGRP receptor subfamily. Journal of medicinal chemistry 31 11689073
2016 Histone deacetylase inhibitors interrupt HSP90•RASGRP1 and HSP90•CRAF interactions to upregulate BIM and circumvent drug resistance in lymphoma cells. Leukemia 30 27890930
2018 Sp1-regulated transcription of RasGRP1 promotes hepatocellular carcinoma (HCC) proliferation. Liver international : official journal of the International Association for the Study of the Liver 28 29655291
2016 RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network ("Rhesactome") in the striatum. Science signaling 28 27902448
2007 Chronic immunodeficiency in mice lacking RasGRP1 results in CD4 T cell immune activation and exhaustion. Journal of immunology (Baltimore, Md. : 1950) 28 17675473
2001 Guanine nucleotide exchange factors CalDAG-GEFI and CalDAG-GEFII are colocalized in striatal projection neurons. The Journal of comparative neurology 28 11503142
2017 Thymic progenitors of TCRαβ+ CD8αα intestinal intraepithelial lymphocytes require RasGRP1 for development. The Journal of experimental medicine 27 28652304
2020 RasGRP1 is a causal factor in the development of l-DOPA-induced dyskinesia in Parkinson's disease. Science advances 26 32426479
2018 Decreased Expression of Serine/Arginine-Rich Splicing Factor 1 in T Cells From Patients With Active Systemic Lupus Erythematosus Accounts for Reduced Expression of RasGRP1 and DNA Methyltransferase 1. Arthritis & rheumatology (Hoboken, N.J.) 26 29905030
2011 Aberrant expression of RasGRP1 cooperates with gain-of-function NOTCH1 mutations in T-cell leukemogenesis. Leukemia 26 22116551
2020 BRD2 induces drug resistance through activation of the RasGRP1/Ras/ERK signaling pathway in adult T-cell lymphoblastic lymphoma. Cancer communications (London, England) 25 32459053
2003 Transgenic expression of RasGRP1 induces the maturation of double-negative thymocytes and enhances the production of CD8 single-positive thymocytes. Journal of immunology (Baltimore, Md. : 1950) 24 12538669
2012 Differential requirement of RasGRP1 for γδ T cell development and activation. Journal of immunology (Baltimore, Md. : 1950) 23 22623331
2007 SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1. Molecular immunology 23 17658605
2004 RasGRP1 sensitizes an immature B cell line to antigen receptor-induced apoptosis. The Journal of biological chemistry 23 14970203
2022 RasGRP1 promotes the acute inflammatory response and restricts inflammation-associated cancer cell growth. Nature communications 22 36385095
2019 RasGRP1 is a potential biomarker to stratify anti-EGFR therapy response in colorectal cancer. JCI insight 22 31237864
2012 Regulation of RasGRP1 function in T cell development and activation by its unique tail domain. PloS one 22 22719950
2004 Synthetic bryostatin analogues activate the RasGRP1 signaling pathway. Journal of medicinal chemistry 22 15588099
2007 Regulation of RasGRP1 by B cell antigen receptor requires cooperativity between three domains controlling translocation to the plasma membrane. Molecular biology of the cell 21 17567957
2007 RasGRP1 overexpression in the epidermis of transgenic mice contributes to tumor progression during multistage skin carcinogenesis. Cancer research 21 17974959
2011 Constitutive abnormal expression of RasGRP-1 isoforms and low expression of PARP-1 in patients with systemic lupus erythematosus. Lupus 20 21976405
2009 RasGRP1 regulates antigen-induced developmental programming by naive CD8 T cells. Journal of immunology (Baltimore, Md. : 1950) 20 20007535
2002 Structural basis of RasGRP binding to high-affinity PKC ligands. Journal of medicinal chemistry 20 11831896
2016 Novel identified associations of RGS1 and RASGRP1 variants in IgA Nephropathy. Scientific reports 19 27804980
2009 Membrane localization of RasGRP1 is controlled by an EF-hand, and by the GEF domain. Biochimica et biophysica acta 19 19168098
2009 RasGRP1 transgenic mice develop cutaneous squamous cell carcinomas in response to skin wounding: potential role of granulocyte colony-stimulating factor. The American journal of pathology 19 19497993
2020 Dysregulated RASGRP1 expression through RUNX1 mediated transcription promotes autoimmunity. European journal of immunology 18 33065764
2015 Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFα inhibitors. Arthritis research & therapy 18 26714738
2014 Targeted deletion of RasGRP1 impairs skin tumorigenesis. Carcinogenesis 18 24464785
2011 Phosphoinositide 3-kinase regulates plasma membrane targeting of the Ras-specific exchange factor RasGRP1. The Journal of biological chemistry 18 21285350
2006 RasGRP1 transmits prodifferentiation TCR signaling that is crucial for CD4 T cell development. Journal of immunology (Baltimore, Md. : 1950) 18 16849453
2019 Mechanistic Characterization of RASGRP1 Variants Identifies an hnRNP-K-Regulated Transcriptional Enhancer Contributing to SLE Susceptibility. Frontiers in immunology 17 31164884
2020 Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells. Cellular microbiology 16 32830401
2016 RasGRP1 Is an Essential Signaling Molecule for Development of B1a Cells with Autoantigen Receptors. Journal of immunology (Baltimore, Md. : 1950) 16 26851222
2011 G alpha i2 and ZAP-70 mediate RasGRP1 membrane localization and activation of SDF-1-induced T cell functions. Journal of immunology (Baltimore, Md. : 1950) 16 21856938
2006 Differential effects of bryostatin 1 and 12-O-tetradecanoylphorbol-13-acetate on the regulation and activation of RasGRP1 in mouse epidermal keratinocytes. Molecular cancer therapeutics 16 16546974
2024 Targeting macrophagic RasGRP1 with catechin hydrate ameliorates sepsis-induced multiorgan dysfunction. Phytomedicine : international journal of phytotherapy and phytopharmacology 15 38759314
2019 High-throughput transcriptome analysis reveals that the loss of Pten activates a novel NKX6-1/RASGRP1 regulatory module to rescue microphthalmia caused by Fgfr2-deficient lenses. Human genetics 15 31691004
2014 Synthesis, biological, and biophysical studies of DAG-indololactones designed as selective activators of RasGRP. Bioorganic & medicinal chemistry 15 24794745
2013 Multiple checkpoint breach of B cell tolerance in Rasgrp1-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 15 23997211
2012 A phospholipase C-γ1-independent, RasGRP1-ERK-dependent pathway drives lymphoproliferative disease in linker for activation of T cells-Y136F mutant mice. Journal of immunology (Baltimore, Md. : 1950) 15 23209318
2011 Parathyroid hormone (PTH) regulates the sodium chloride cotransporter via Ras guanyl releasing protein 1 (Ras-GRP1) and extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein kinase (MAPK) pathway. Translational research : the journal of laboratory and clinical medicine 15 22005268
2008 Adaptor SKAP-55 binds p21 activating exchange factor RasGRP1 and negatively regulates the p21-ERK pathway in T-cells. PloS one 15 18320039
2000 Distribution of ras guanyl releasing protein (RasGRP) mRNA in the adult rat central nervous system. Journal of neurocytology 14 11279364
2013 RasGRP1, but not RasGRP3, is required for efficient thymic β-selection and ERK activation downstream of CXCR4. PloS one 13 23308188
2016 RasGRP1 and RasGRP3 Are Required for Efficient Generation of Early Thymic Progenitors. Journal of immunology (Baltimore, Md. : 1950) 12 27465532
2010 RasGRP1 is essential for ras activation by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in epidermal keratinocytes. The Journal of biological chemistry 12 20308057
2019 RasGRP1 is a target for VEGF to induce angiogenesis and involved in the endothelial-protective effects of metformin under high glucose in HUVECs. IUBMB life 11 31120617
2021 Nras Q61R/+ and Kras-/- cooperate to downregulate Rasgrp1 and promote lympho-myeloid leukemia in early T-cell precursors. Blood 10 33512434
2017 Exploring the influence of indololactone structure on selectivity for binding to the C1 domains of PKCα, PKCε, and RasGRP. Bioorganic & medicinal chemistry 10 28392275
2016 Autoantibody-Mediated Pulmonary Alveolar Proteinosis in Rasgrp1-Deficient Mice. Journal of immunology (Baltimore, Md. : 1950) 9 27279372
2006 RasGRP1 confers the phorbol ester-sensitive phenotype to EL4 lymphoma cells. Molecular pharmacology 9 17065239
1999 RasGRP, a Ras activator: mouse and human cDNA sequences and chromosomal positions. Mammalian genome : official journal of the International Mammalian Genome Society 9 10087292

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