| 2002 |
ARAP1 has PIP3-dependent Arf GAP activity and Rho GAP activity in vitro; it associates with the Golgi; Rho GAP activity mediates cell rounding and loss of stress fibers; Arf GAP activity mediates Golgi changes and filopodia formation via increased Cdc42 activity; both activities contribute to inhibiting cell spreading. |
In vitro GAP assays, overexpression with functional readouts (cell rounding, stress fibers, filopodia), Golgi localization by imaging |
Molecular cell |
High |
11804590
|
| 2003 |
ARAP1 (493-aa isoform identified by yeast two-hybrid) binds the C-terminal region of the angiotensin II type 1A receptor (AT1A) and promotes recycling of internalized AT1A to the plasma membrane in HEK-293 cells, co-localizing with recycled AT1A at the membrane 45 min after Ang II treatment. |
Yeast two-hybrid, co-immunoprecipitation, immunocytochemistry, functional Ca2+ release assay |
Biochemical and biophysical research communications |
Medium |
14559250
|
| 2008 |
ARAP1 is recruited transiently to Rab5-positive, EEA1-negative early endocytic puncta containing EGFR upon EGF stimulation; knockdown of ARAP1 accelerates EGF association with EEA1 endosomes and EGFR degradation, and reduces duration of ERK and JNK phosphorylation, indicating ARAP1 controls an early endocytic checkpoint to delay EGFR signal attenuation. |
siRNA knockdown, live/fixed imaging with Rab5/EEA1/rabaptin-5 markers, EGFR degradation assay, ERK/JNK phosphorylation time course |
Traffic (Copenhagen, Denmark) |
High |
18939958
|
| 2008 |
ARAP1 localizes to Golgi and endosomal compartments, enriched in internal membranes of multivesicular bodies; its distribution is controlled by phosphorylation and by binding to 3- and 4-phosphorylated phosphoinositides through its PH domains; ARAP1 knockdown causes EGFR accumulation in sorting/late endosomes and inhibits EGFR degradation with prolonged downstream signaling. |
Subcellular fractionation, immunofluorescence, siRNA knockdown, EGFR trafficking/degradation assay, phosphorylation analysis |
Traffic (Copenhagen, Denmark) |
High |
18764928
|
| 2009 |
The first PH domain (PH1) of ARAP1 specifically binds PtdIns(3,4,5)P3 with ~1.6 µM affinity; this binding allosterically stimulates Arf GAP catalytic activity without mediating membrane recruitment; PtdIns(3,4,5)P3 binding to PH1 is required for ARAP1 function as a regulator of EGFR endocytic trafficking in cells. |
Lipid-binding assays (in vitro), in vitro GAP activity assay with PH domain mutants, membrane recruitment assay in cells, EGFR trafficking assay with PH mutants |
The Journal of biological chemistry |
High |
19666464
|
| 2010 |
PTK6 (Brk) directly phosphorylates ARAP1 at Tyr231; this phosphorylation is EGF/EGFR-dependent and requires the SH2 domain (Arg105) of PTK6; phosphorylated ARAP1 inhibits EGFR down-regulation, whereas the Y231F mutant of ARAP1 does not, linking PTK6-mediated phosphorylation of ARAP1 to sustained EGFR signaling in breast cancer cells. |
Co-immunoprecipitation, MALDI-TOF mass spectrometry, in vitro/cell-based phosphorylation assay, site-directed mutagenesis (Y231F), EGFR degradation assay, PTK6 siRNA knockdown |
The Journal of biological chemistry |
High |
20554524
|
| 2011 |
ARAP1 associates with CIN85 via its PXPXXRX motif (Arg86/Arg90) interacting with CIN85 SH3 domains; this interaction is required for ARAP1-dependent routing of EGFR away from the EEA1-positive early endosome; ARAP1 overexpression reduces Cbl-mediated EGFR ubiquitination and slows Cbl-dependent EGFR degradation, and a CIN85-binding-deficient ARAP1 mutant fails to rescue EGFR trafficking. |
Co-immunoprecipitation, mutagenesis, siRNA knockdown (ARAP1 and CIN85), EGFR ubiquitination assay, EGFR degradation assay |
Biology of the cell |
High |
21275903
|
| 2012 |
ARAP1 is recruited to circular dorsal ruffles (CDRs) upon growth factor stimulation and increases CDR ring size in an Arf GAP activity-dependent manner; dominant-negative Arf1 and Arf5 expand CDR size, placing Arf1 and Arf5 downstream of ARAP1 in CDR ring size control. |
Overexpression/knockdown with live imaging and phalloidin staining, dominant-negative Arf constructs, Arf GAP-dead ARAP1 mutants |
Molecular biology of the cell |
High |
22573888
|
| 2013 |
Arap1-deficient mice show reduced vascular sensitivity to angiotensin II (demonstrated in isolated perfused kidney), accelerated sepsis-induced hypotension, and increased plasma renin concentration, consistent with ARAP1 promoting AT1 receptor surface expression in vascular smooth muscle/mesangial cells in vivo. |
Arap1 knockout mouse, isolated perfused kidney vascular resistance assay, telemetric blood pressure, LPS endotoxemia model |
Critical care (London, England) |
High |
23844607
|
| 2008 |
ARAP1 interacts with the intracellular part of TRAIL death receptor DR4 (identified by yeast two-hybrid); ARAP1 co-precipitates with DR4 and co-localizes with it in the ER/Golgi, plasma membrane, and early endosomes; ARAP1 knockdown significantly reduces DR4 cell-surface localization in tumor cell lines and slows TRAIL-induced death. |
Yeast two-hybrid, co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown, flow cytometry for surface DR4, cell death assay |
Apoptosis : an international journal on programmed cell death |
Medium |
18165900
|
| 2018 |
In osteoclasts, ARAP1 is part of a podosome/sealing zone complex where its RhoGAP domain regulates actin dynamics; at endosomes, ARAP1 interacts with AP-3 adaptor complexes and its Arf-GAP domain regulates Arf1-dependent AP-3 membrane binding, controlling lysosomal membrane protein transport to ruffled borders; ARAP1 or AP-3 depletion reduces osteoclast bone-digesting capacity in vitro, and AP-3δ-deficient mocha mice develop osteoporosis. |
Co-immunoprecipitation, domain-specific mutants, siRNA knockdown, bone resorption assay, mouse model (mocha) |
iScience |
High |
30240610
|
| 2018 |
Crystal structure and biochemical analysis revealed that the CIN85 SH3B domain binds the ARAP1 PXPXXRX(except P)XXR/H/K motif with high affinity and specificity; the β2-β3 loops of CIN85 SH3 domains and H87ARAP1/E132CIN85 interaction confer binding specificity; ARAP1 competes with Cbl for CIN85 binding, providing a structural basis for ARAP1-mediated attenuation of EGFR internalization. |
Crystal structure determination, ITC, analytical gel-filtration chromatography, mutagenesis, domain-swapping |
Biochemistry |
High |
29589748
|
| 2017 |
Arap1 knockout mice develop photoreceptor degeneration starting at 4 weeks; Arap1 is expressed in Müller glia (not photoreceptors), implicating a non-cell-autonomous role of ARAP1 in photoreceptor survival via Müller glia. |
Knockout mouse, OCT imaging, fundus photography, immunohistochemistry, electroretinography |
Investigative ophthalmology & visual science |
Medium |
28324111
|
| 2022 |
Conditional knockout of Arap1 in RPE (using Vmd2-Cre) but not in Müller glia (Glast-Cre) recapitulates the photoreceptor degeneration phenotype; Arap1-/- RPE shows a clear phagocytic defect in vivo; mass spectrometry of ARAP1 co-IP identified candidate binding partners involved in phagocytosis, cytoskeletal organization, and intracellular trafficking. |
Conditional knockout mouse (cell-type-specific Cre lines), outer-segment phagocytosis quantification in vivo, co-immunoprecipitation mass spectrometry |
Disease models & mechanisms |
High |
35758026
|
| 2023 |
ARAP1 overexpression significantly inhibits migration and invasion of lung adenocarcinoma cells in vitro and in vivo; an Arf-GAP-dead mutant does not rescue, whereas RhoGAP activity is responsible for suppressing stress fiber formation and thereby metastasis. |
Overexpression with RhoGAP-dead mutant controls, stress fiber imaging, Transwell migration/invasion assay, in vivo xenograft |
Discover oncology |
Medium |
38008882
|
| 2025 |
ARAP1 modulates RhoA activity at cell protrusions via its RA domain, which binds Rap1 and Rac1; ARAP1-deficient lymphocytes show enhanced chemokine-directed migration with increased RhoA activation and F-actin polymerization; ARAP1 overexpression inhibits migration in a RhoGAP-domain-dependent manner; the RA domain binding of Rap1/Rac1 is required for ARAP1-mediated RhoA inhibition. |
ARAP1 knockout/overexpression, Rho biosensor imaging, F-actin measurement, RA-domain mutants, Rap1/Rac1 binding assay, chemotaxis assay |
Frontiers in immunology |
High |
41488654
|
| 2014 |
The T2D-risk allele (C) of rs11603334, near an ARAP1 promoter, shows ~2-fold higher transcriptional activity in reporter assays and reduced binding of transcriptional regulators PAX6 and PAX4 in EMSA; the C allele is associated with increased ARAP1 mRNA in human pancreatic islet samples, suggesting PAX6/PAX4-mediated repression normally limits ARAP1 expression in beta cells. |
Luciferase reporter assay in pancreatic beta cell lines, EMSA, allele-specific mRNA quantification in human islets |
American journal of human genetics |
Medium |
24439111
|
| 2020 |
ARAP1 maintains persistent EGFR activation in high-glucose-treated HK-2 cells by reducing EGFR ubiquitination through competing with Cbl for CIN85 binding; lncRNA ARAP1-AS2 directly interacts with ARAP1 protein (RNA pulldown), promoting this mechanism to activate TGF-β/Smad3 signaling and fibrosis. |
RNA pulldown, co-immunoprecipitation, ubiquitination assay, dual-immunofluorescence, EGFR signaling assay, siRNA/overexpression |
Journal of cellular and molecular medicine |
Medium |
32969198
|
| 2025 |
In Hep3B hepatocellular carcinoma cells, ARAP1 localizes to CDRs and mitochondria (not observed in control HCC lines); ARAP1 KO reduces CDR size, disrupts lamellipodia architecture, attenuates macropinocytic nutrient uptake, and reduces cell growth and invasive potential; ARAP1 is actively degraded via proteasome in Hep3B cells, explaining its lower absolute level despite pro-CDR function. |
ARAP1 CRISPR KO, confocal microscopy, high-resolution SEM, proteasome inhibitor (MG132), macropinocytosis assay, cell proliferation and Transwell assays |
Cell communication and signaling : CCS |
Medium |
39934854
|