Affinage

RASA1

Ras GTPase-activating protein 1 · UniProt P20936

Length
1047 aa
Mass
116.4 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 20 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

RASA1 (p120RasGAP) is a multi-domain GTPase-activating protein that terminates Ras signaling by accelerating GTP hydrolysis on Ras, with its catalytic GAP domain forming a shallow groove that engages Ras·GTP (PMID:8955277). Its activity is regulated by tyrosine phosphorylation: oncogenic and receptor tyrosine kinases (v-src, v-fps, EGFR, bcr/abl) and cytokine receptors (erythropoietin) phosphorylate RASA1 and inhibit its GAP activity, permitting Ras activation, while its SH2 domains recruit it into phosphotyrosine-dependent complexes (PMID:1689011, PMID:1569084, PMID:8195713). RASA1 is dynamically targeted to membranes and adhesion sites: annexin A6 directs Ca2+-dependent plasma membrane localization that restrains Ras/Raf activation (PMID:15940262), and integrin- and FAK-mediated cues recruit RASA1 with p190RhoGAP to focal adhesions, where SH2-mediated binding to FAK (at Tyr397) drives p190RhoGAP activation and establishes cell polarity during migration (PMID:9690509, PMID:16971514, PMID:19435801). This coupling extends to neuronal guidance, where RGMa-neogenin signaling dephosphorylates FAK Y397 to release RASA1 onto Ras and mediate growth cone collapse (PMID:19458235). RASA1 also bridges Ras and Rho regulation through its SH3 domain, which inhibits the RhoGAP activity of DLC1-3 by targeting their catalytic arginine finger (PMID:24443565), and regulates integrin recycling by competing with Rab21 for endocytosed integrin α-subunits via its GAP domain (PMID:21768288). In the vasculature, RASA1 acts as a critical effector of EPHB4 to suppress mTORC1 (PMID:24837431), is required for lymphatic valve endothelial cell survival in a catalytic-activity-dependent manner (PMID:28530642), and enables collagen IV export from the ER during angiogenesis by restraining Ras-MAPK signaling (PMID:31185000). As a RAS/MAPK suppressor, RASA1 cooperates with NF1 to limit RAS signaling, and its expression is controlled by the PITX1/PTP1B axis transcriptionally and by miR-132 post-transcriptionally (PMID:26840794, PMID:29127119, PMID:20676106).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1990 High

    Established that RASA1 is a substrate and binding partner of tyrosine kinases, defining how its SH2-containing complex links growth factor and oncogene signaling to Ras.

    Evidence Tyrosine phosphorylation assay and co-IP in v-src/v-fps-transformed and EGF-stimulated cells, identifying co-precipitating p62 and p190

    PMID:1689011

    Open questions at the time
    • Functional consequence of phosphorylation on GAP activity not directly measured here
    • Identity of p62/p190 not molecularly resolved
  2. 1992 Medium

    Showed that tyrosine phosphorylation of RASA1 functionally inhibits its GAP activity, providing a mechanism for receptor-driven Ras activation.

    Evidence In vitro GTP hydrolysis assay with phosphorylation analysis after erythropoietin stimulation of HEL cells

    PMID:1569084

    Open questions at the time
    • Correlative link between phosphorylation and GAP inhibition, not causal residue mapping
    • Single cell-lysate-based activity readout
  3. 1994 Medium

    Extended the kinase-regulation model to leukemogenic bcr/abl, demonstrating reversible suppression of RASA1 GAP activity tied to Ras activation.

    Evidence GTPase activity assay with antisense knockdown of p210bcr/abl in CML cells

    PMID:8195713

    Open questions at the time
    • Mechanism connecting kinase activity to GAP inhibition not defined
    • Single lab
  4. 1996 High

    Provided the structural basis for catalysis, revealing the Ras·GTP interaction surface on the GAP domain.

    Evidence X-ray crystallography of GAP-334 with functional mapping of conserved residues

    PMID:8955277

    Open questions at the time
    • No co-crystal with Ras in this structure
    • Regulatory domains outside GAP not structurally characterized
  5. 1996 Medium

    Identified the CaLB/C2 domain as a membrane-targeting module through direct annexin VI binding.

    Evidence In vitro binding with isolated CaLB domain and co-IP in rat fibroblasts

    PMID:8798684

    Open questions at the time
    • Functional consequence for Ras signaling not tested here
    • Single lab
  6. 1998 Medium

    Demonstrated integrin-driven relocalization of RASA1 with p190RhoGAP and FAK to cytoskeletal signaling complexes, linking adhesion to Ras/Rho regulation.

    Evidence Subcellular fractionation and Western blot after plating on ECM proteins

    PMID:9690509

    Open questions at the time
    • Fractionation-based, no direct imaging of complex
    • Functional output of recruitment not assessed
  7. 1998 Medium

    Placed RASA1 in a CD4/lck-dependent signaling complex with Sam68 and PLCγ1 in T cells.

    Evidence Co-IP across CD4+/CD4- T cell lines and CD4/lck-binding mutants

    PMID:9743338

    Open questions at the time
    • Direct binding partner within the complex not resolved
    • Downstream signaling consequence untested
  8. 2001 Medium

    Defined PH and C2/CaLB domains as a docking site for the PKC scaffold RACK1, regulated by Ser/Thr phosphorylation.

    Evidence In vitro pulldown with domain-deletion mutants and recombinant RACK1 plus co-IP

    PMID:11350068

    Open questions at the time
    • Functional role of RACK1-RASA1 complex unknown
    • Single lab
  9. 2005 Medium

    Established annexin A6 as a Ca2+-dependent driver of RASA1 membrane targeting that dampens Ras/Raf-1 activation.

    Evidence Live-cell imaging, in vitro membrane binding, RNAi knockdown, and Ras activation assay

    PMID:15940262

    Open questions at the time
    • Quantitative contribution of annexin A6 versus other targeting modules unresolved
    • Single lab
  10. 2006 High

    Showed that integrin/Arg-kinase signaling activates p190RhoGAP through RASA1 binding and peripheral recruitment, coupling RASA1 to Rho inactivation.

    Evidence In vitro RhoGAP assay, dominant-negative p120 fragment, co-IP, and immunofluorescence

    PMID:16971514

    Open questions at the time
    • p120 binding does not directly activate p190 in vitro; the activating step remains indirect
    • Precise localization signal not defined
  11. 2009 High

    Resolved how FAK assembles a RASA1/p190RhoGAP complex at leading-edge adhesions to set cell polarity during migration.

    Evidence Co-IP, siRNA knockdown, FAK Y397 mutation, and wound-healing/Golgi reorientation assays

    PMID:19435801

    Open questions at the time
    • Relative contribution of RasGAP versus scaffolding function in polarity not separated
    • Ras-GTP changes not directly measured
  12. 2009 High

    Demonstrated dynamic FAK-RASA1 dissociation as the switch that converts RGMa-neogenin signaling into Ras and Akt inactivation and growth cone collapse.

    Evidence siRNA knockdown with functional rescue, co-IP, phosphorylation assays, growth cone collapse assay in cortical neurons

    PMID:19458235

    Open questions at the time
    • Direct measurement of RASA1-Ras complex stoichiometry absent
    • In vivo relevance to axon guidance not tested here
  13. 2010 High

    Placed RASA1 directly downstream of miR-132 as the effector of an angiogenic switch in endothelial cells.

    Evidence miRNA overexpression/antagomir, Rasa1 conditional knockout, miRNA-resistant RASA1 rescue, and retinal vascular assay

    PMID:20676106

    Open questions at the time
    • Other miR-132 targets contributing to angiogenesis not excluded
    • Mechanism downstream of Ras in this context not detailed
  14. 2011 High

    Uncovered a non-catalytic role: RASA1 promotes integrin recycling by competing with Rab21 for endocytosed integrin α-subunits via its GAP domain.

    Evidence siRNA knockdown, co-IP, integrin recycling and competitive binding assays

    PMID:21768288

    Open questions at the time
    • Whether GAP catalytic activity is required for the recycling function unresolved
    • In vivo physiological role not addressed
  15. 2014 High

    Defined an EPHB4/RASA1/mTORC1 endothelial signaling axis, showing RASA1 as the key EPHB4 effector suppressing mTORC1 for vessel formation.

    Evidence Zebrafish genetic models, engineered RASA1-binding-impaired EPHB4 receptors, and mTORC1 pharmacological rescue

    PMID:24837431

    Open questions at the time
    • Molecular link from RASA1 to mTORC1 suppression not detailed
    • Reliance on zebrafish for in vivo conclusions
  16. 2014 High

    Revealed an atypical SH3-mediated cross-talk in which RASA1 inhibits DLC1-3 RhoGAP activity, functionally linking Ras and Rho pathway regulation.

    Evidence Biochemical RhoGAP activity assay with structural/mutational analysis of the catalytic arginine finger

    PMID:24443565

    Open questions at the time
    • Cellular consequences of DLC inhibition by RASA1 not established here
    • Physiological contexts for this cross-talk unknown
  17. 2016 Medium

    Identified transcriptional control of RASA1 through the PTP1B/PITX1 axis, with PTP1B dephosphorylation destabilizing PITX1 and lowering RASA1 expression.

    Evidence In vitro dephosphorylation assay with site-specific PITX1 mutants, luciferase reporter, and siRNA knockdown

    PMID:26840794

    Open questions at the time
    • Direct PITX1 occupancy of the RASA1 promoter not shown
    • Single lab
  18. 2017 High

    Demonstrated that RasGAP catalytic activity is essential for lymphatic valve endothelial cell survival and valve function.

    Evidence Inducible conditional knockout and catalytically inactive R780Q knock-in mice with lymphatic functional assays

    PMID:28530642

    Open questions at the time
    • Upstream receptor driving this requirement not defined here
    • Molecular cause of valve cell death not detailed
  19. 2017 Medium

    Established RASA1 as a tumor-suppressive RAS regulator cooperating with NF1, with restoration reducing MAPK/PI3K signaling.

    Evidence shRNA knockdown, ectopic re-expression, and MEK inhibitor sensitivity in bronchial epithelial and NSCLC cells

    PMID:29127119

    Open questions at the time
    • Mechanism of RASA1-NF1 cooperativity not resolved
    • Single lab
  20. 2019 High

    Linked RASA1 loss to ER retention of collagen IV via dysregulated Ras-MAPK, explaining endothelial cell death in vascular development.

    Evidence Multiple conditional knockout mouse models with pharmacological rescue (4-PBA, MAPK inhibitors) and ER retention assays

    PMID:31185000

    Open questions at the time
    • How Ras-MAPK signaling impairs collagen IV folding mechanistically unresolved
    • Generality beyond collagen IV not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RASA1's catalytic, scaffolding, and membrane-targeting functions are integrated and selectively deployed across distinct vascular, lymphatic, neuronal, and immune contexts remains unresolved.
  • No unified model distinguishing GAP-dependent versus GAP-independent roles in vivo
  • Direct structural basis for RASA1 regulation by phosphorylation absent
  • Mechanistic link from RASA1 to mTORC1 and to collagen IV folding unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 2 GO:0005768 endosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 2 R-HSA-1474244 Extracellular matrix organization 1
Partners
ANXA6ARHGAP35DLC1EPHB4FAKITGA1KHDRBS1RACK1
Complex memberships
FAK-RASA1-p190RhoGAP focal adhesion complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Crystal structure of the GTPase-activating domain of human p120GAP (GAP-334) was solved, revealing it as an elongated, exclusively helical protein with a novel fold consisting of two domains. Conserved residues around a shallow groove in the central domain identify the Ras·GTP interaction site, providing a structural model for how GAP accelerates GTP hydrolysis by Ras. X-ray crystallography Nature High 8955277
1990 RASA1 (p120GAP) is phosphorylated on tyrosine in cells transformed by cytoplasmic and receptor-like tyrosine kinases (v-src, v-fps) and in fibroblasts stimulated with EGF. Two co-precipitating proteins, p62 and p190, are also tyrosine-phosphorylated under the same conditions, indicating that tyrosine kinases interact with the RASA1 complex through its SH2 domains. Tyrosine phosphorylation assay, co-immunoprecipitation, inducible oncogene expression system Nature High 1689011
1992 Erythropoietin stimulation of HEL cells induces rapid tyrosine phosphorylation of p120GAP (RASA1), correlating with activation of p21ras (increased GTP loading) and reduced GTPase-promoting activity of cell lysates in vitro, suggesting that tyrosine phosphorylation of RASA1 inhibits its GAP activity and thereby allows Ras activation downstream of the erythropoietin receptor. In vitro GTP hydrolysis assay, tyrosine phosphorylation analysis, anti-RASA1 immunoprecipitation The Journal of biological chemistry Medium 1569084
1994 p210bcr/abl tyrosine kinase expression in fibroblasts simultaneously activates p21ras and inhibits the GTPase-promoting activity of p120GAP (RASA1). Conversely, downregulation of p210bcr/abl in CML cells with antisense oligonucleotides restores RASA1 GTPase-promoting activity and inhibits Ras activation. Tyrosine phosphorylation of p190 and p62 (RASA1-associated proteins) depends on bcr/abl kinase activity. GTPase activity assay, antisense oligonucleotide knockdown, transient expression The Journal of experimental medicine Medium 8195713
1996 The CaLB (Ca2+-dependent lipid binding) domain of p120GAP (RASA1) mediates a direct protein-protein interaction with annexin VI (p70). This interaction was demonstrated in vitro using the isolated CaLB domain and confirmed by co-immunoprecipitation in rat fibroblasts, suggesting the CaLB domain directs calcium-dependent membrane association of RASA1 through binding to annexin VI. In vitro binding assay with isolated CaLB domain, co-immunoprecipitation The Journal of biological chemistry Medium 8798684
1998 In mouse fibroblasts undergoing integrin-mediated cell-substrate interaction, p120RasGAP (RASA1) and its associated protein p190RhoGAP are rapidly recruited to the cytoskeleton together with focal adhesion kinase (p125FAK). This recruitment occurs upon plating on ECM proteins such as fibronectin, indicating integrin-mediated relocalization of RASA1 to cytoskeletal signaling complexes. Subcellular fractionation, Western blot, integrin-mediated adhesion assay Oncogene Medium 9690509
1998 Sam68 associates with p120GAP (RASA1) and PLCγ1 in mature human CD4+ T cells. This association is dependent on CD4 expression and partially dependent on the association of CD4 with p56lck, as demonstrated by reduced Sam68-RASA1 co-precipitation in CD4-negative mutants and in cells expressing a CD4 mutant unable to interact with p56lck. Co-immunoprecipitation in CD4+/CD4- T cell lines and CD4 mutants Journal of immunology Medium 9743338
2001 RACK1 (a PKC scaffolding protein) interacts with p120GAP (RASA1) in a manner dependent on both the PH and C2/CaLB domains of RASA1. A fusion protein containing the GAP PH domain directly bound recombinant RACK1 in vitro, and co-immunoprecipitation confirmed the in vivo association. Serine/threonine phosphorylation regulates this interaction. Co-immunoprecipitation, in vitro pulldown with domain deletion mutants and recombinant proteins Biochemical and biophysical research communications Medium 11350068
2005 Annexin A6 promotes plasma membrane targeting of p120GAP (RASA1) in a Ca2+-dependent manner in living cells and stimulates membrane binding of RASA1 in vitro. Annexin A6 expression reduces HDL- and EGF-induced Ras and Raf-1 activation, and this effect is mediated via RASA1, as RNAi-mediated reduction of RASA1 levels showed enhanced Ras activation particularly in annexin A6-expressing cells. Live cell imaging, in vitro membrane binding assay, RNAi knockdown, Ras activation assay Oncogene Medium 15940262
2006 Integrin signaling through the Arg tyrosine kinase activates p190RhoGAP by promoting its binding to p120RasGAP (RASA1) and recruitment to the cell periphery. p190 requires its p120-binding domain for Arg-dependent activation in vivo; however, p120 binding does not directly activate p190RhoGAP activity in vitro. A dominant-negative p120 fragment blocks p190:p120 complex formation, prevents p190 activation, and disrupts adhesion-dependent recruitment of p190 to the cell periphery. In vitro RhoGAP activity assay, dominant-negative p120 fragment, co-immunoprecipitation, immunofluorescence localization Molecular biology of the cell High 16971514
2009 FAK promotes cell polarity during migration by forming a complex with p120RasGAP (RASA1) and p190RhoGAP (p190A) at leading-edge focal adhesions. Fibronectin-integrin-mediated FAK activation promotes SH2-mediated binding of RASA1 to FAK, and this FAK-RASA1 association facilitates FAK-mediated p190A tyrosine phosphorylation. Knockdown of RASA1, mutation of FAK Y397, or inhibition of FAK activity all prevented FAK-p190A association, p190A phosphorylation, and cell polarity. Co-immunoprecipitation, siRNA knockdown, FAK Y397 mutation, wound-healing and Golgi reorientation assays Journal of cell science High 19435801
2009 RGMa binding to its receptor neogenin leads to dephosphorylation of FAK at Tyr-397, which dissociates RASA1 (p120GAP) from FAK. This dissociation increases the interaction between RASA1 and GTP-Ras, leading to Ras inactivation. Knockdown of RASA1 prevents RGMa-induced growth cone collapse and neurite outgrowth inhibition in cortical neurons. RGMa also inactivates Akt through RASA1, and constitutively active Akt rescues RGMa-induced growth cone collapse. siRNA knockdown, co-immunoprecipitation, phosphorylation assays, growth cone collapse assay The Journal of neuroscience High 19458235
2010 miR-132 suppresses p120RasGAP (RASA1) expression in endothelial cells, leading to increased Ras activity and induction of neovascularization. A miRNA-resistant version of p120RasGAP reversed the vascular response induced by miR-132. Anti-miR-132 inhibited angiogenesis in wild-type mice but not in mice with inducible deletion of Rasa1, placing RASA1 directly downstream of miR-132 as the effector of the angiogenic switch. miRNA overexpression/antagomir, Rasa1 conditional knockout, rescue with miRNA-resistant RASA1, retinal vascular assay Nature medicine High 20676106
2011 p120RasGAP (RASA1) regulates recycling of endocytosed α/β1-integrin heterodimers to the plasma membrane. RASA1 interacts with the cytoplasmic domain of integrin α-subunits via its GAP domain and competes with Rab21 for binding to endocytosed integrins, facilitating exit of integrins from Rab21- and EEA1-positive endosomes. Silencing of RASA1 attenuated integrin recycling and augmented cell motility. siRNA knockdown, co-immunoprecipitation, integrin recycling assay, competitive binding assay The Journal of cell biology High 21768288
2014 RASA1 functions as a critical effector downstream of the endothelial receptor EPHB4. In zebrafish, RASA1 or EPHB4 deficiency produce similar vascular abnormalities, and engineered EPHB4 receptors with impaired RASA1-binding fail to rescue blood flow in EPHB4-deficient animals. EPHB4 deficiency leads to robust mTORC1 overactivation, and pharmacological mTORC1 inhibition rescues vessel structure and function, defining an EPHB4/RASA1/mTORC1 signaling axis in endothelial cells. Zebrafish genetic models, engineered receptor rescue, mTORC1 pharmacological inhibition, tissue lysate signaling analysis The Journal of clinical investigation High 24837431
2014 The SH3 domain of p120RasGAP (RASA1) selectively inhibits the RhoGAP activity of all three DLC isoforms (DLC1-3) by targeting the catalytic arginine finger of the DLC RhoGAP domain, thereby competitively inhibiting RhoGAP activity. This represents an atypical SH3 interaction not following the classical PXXP motif. This cross-talk functionally connects Ras and Rho regulatory pathways. Biochemical RhoGAP activity assay, structural/mutational analysis, SH3 domain competition assay The Journal of biological chemistry High 24443565
2016 PTP1B directly dephosphorylates the transcription factor PITX1 at Y160, Y175, and Y179, reducing its protein stability and transcriptional activity toward the RASA1 gene. PTP1B inhibition or silencing upregulates the PITX1-p120RasGAP axis. Sorafenib decreases PTP1B activity, promoting PITX1 hyperphosphorylation and increased RASA1 expression. In vitro dephosphorylation assay, siRNA knockdown, luciferase reporter assay, molecular docking Hepatology Medium 26840794
2017 RASA1 regulates the function of lymphatic vessel valves; catalytic (RasGAP) activity is essential for this function. Disruption of Rasa1 in adult mice resulted in loss of lymphatic endothelial cells specifically from collecting lymphatic vessel valve leaflets, preventing backflow prevention and impairing vessel pumping. A catalytically inactive RASA1(R780Q) mutant phenocopied Rasa1 deletion, demonstrating that RasGAP catalytic activity is required. Inducible conditional knockout mice, catalytically inactive knock-in mutant (R780Q), lymphatic vessel functional assays The Journal of clinical investigation High 28530642
2017 RASA1 knockdown in human bronchial epithelial cells activates signaling downstream of RAS and promotes cell growth. Restoration of RASA1 expression in RASA1-mutated NSCLC cells reduces MAPK and PI3K signaling. Concurrent genetic silencing of RASA1 and NF1 profoundly sensitizes cells to MEK inhibition (trametinib), indicating that RASA1 and NF1 cooperatively suppress RAS/MAPK signaling. shRNA knockdown, ectopic re-expression, MEK inhibitor sensitivity assay, signaling pathway analysis Clinical cancer research Medium 29127119
2019 RASA1 is required in endothelial cells for the export of collagen IV and its deposition in vascular basement membranes during developmental angiogenesis. In the absence of RASA1, dysregulated Ras-MAPK signaling causes impaired folding of collagen IV and its retention in the ER, leading to endothelial cell death. Chemical chaperone 4-PBA and MAPK inhibitors rescued ER retention of collagen IV and EC apoptosis, restoring normal angiogenesis. Multiple conditional knockout mouse models, pharmacological rescue (4-PBA, MAPK inhibitors, collagen-modifying enzyme inhibitors), ER retention assay The Journal of clinical investigation High 31185000

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Gap junctions and the connexin protein family. Cardiovascular research 774 15094343
1990 Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases. Nature 739 1689011
2009 Gap junctions. Cold Spring Harbor perspectives in biology 490 20066080
2004 The effects of connexin phosphorylation on gap junctional communication. The international journal of biochemistry & cell biology 489 15109565
2000 Regulation of gap junctions by phosphorylation of connexins. Archives of biochemistry and biophysics 435 11368307
2010 MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nature medicine 433 20676106
2003 Rheb fills a GAP between TSC and TOR. Trends in biochemical sciences 393 14607085
2012 Gap junctions. Comprehensive Physiology 317 23723031
2000 Gap junctions in cardiovascular disease. Circulation research 304 10864907
2018 Bridging the Gap between Connectome and Transcriptome. Trends in cognitive sciences 301 30455082
2002 Gap junctions and ovarian folliculogenesis. Reproduction (Cambridge, England) 263 12006089
2006 IQGAP1 in cellular signaling: bridging the GAP. Trends in cell biology 256 16595175
2013 RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation. Human mutation 226 24038909
1989 Gap junctional communication and development. Trends in neurosciences 216 2471332
2010 The gap gene network. Cellular and molecular life sciences : CMLS 202 20927566
1993 Gap junction function and cancer. Cancer research 200 8393376
2017 DNA Fiber Analysis: Mind the Gap! Methods in enzymology 195 28645379
2008 Gap junctions couple astrocytes and oligodendrocytes. Journal of molecular neuroscience : MN 188 18236012
2009 Plasmodesmata - bridging the gap between neighboring plant cells. Trends in cell biology 187 19748270
2005 RASA1: variable phenotype with capillary and arteriovenous malformations. Current opinion in genetics & development 186 15917201
2001 Innexins get into the gap. BioEssays : news and reviews in molecular, cellular and developmental biology 180 11340620
2004 Pathways for degradation of connexins and gap junctions. Cardiovascular research 153 15094346
1996 Crystal structure of the GTPase-activating domain of human p120GAP and implications for the interaction with Ras. Nature 148 8955277
1999 Role of connexin (gap junction) genes in cell growth control and carcinogenesis. Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie 140 10196667
1992 Erythropoietin induces p21ras activation and p120GAP tyrosine phosphorylation in human erythroleukemia cells. The Journal of biological chemistry 132 1569084
2006 Gap junctions and cochlear homeostasis. The Journal of membrane biology 127 16773501
1997 Metabolic trafficking through astrocytic gap junctions. Glia 127 9298854
2009 A FAK-p120RasGAP-p190RhoGAP complex regulates polarity in migrating cells. Journal of cell science 120 19435801
1992 Biophysics of gap junctions. Seminars in cell biology 117 1320429
2002 Gap junctions, homeostasis, and injury. Journal of cellular physiology 115 12012322
2000 Gap junctions in the nervous system. Brain research. Brain research reviews 112 10928802
2006 Downregulation of gap junctions in cancer cells. Critical reviews in oncogenesis 111 17425504
2006 Integrin signaling through Arg activates p190RhoGAP by promoting its binding to p120RasGAP and recruitment to the membrane. Molecular biology of the cell 103 16971514
1985 Regulation of gap junctional conductance. The American journal of physiology 103 2408489
2016 Mechanics of epithelial tissues during gap closure. Current opinion in cell biology 99 27131272
2018 MicroRNA-223 Regulates Cardiac Fibrosis After Myocardial Infarction by Targeting RASA1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 98 29689569
1995 Gap junctions in the vertebrate retina. Microscopy research and technique 98 8534902
2016 SYNGAP1: Mind the Gap. Frontiers in cellular neuroscience 97 26912996
2007 Gap junctional communication in morphogenesis. Progress in biophysics and molecular biology 97 17481700
1994 Negative regulation of p120GAP GTPase promoting activity by p210bcr/abl: implication for RAS-dependent Philadelphia chromosome positive cell growth. The Journal of experimental medicine 96 8195713
2002 Gap junctions and motor behavior. Trends in neurosciences 90 11814564
1997 Ras-GTPase activating protein (GAP): a putative effector for Ras. Cellular signalling 89 9113414
2014 Roles of gap junctions, connexins, and pannexins in epilepsy. Frontiers in physiology 88 24847276
2013 Lymphatic abnormalities are associated with RASA1 gene mutations in mouse and man. Proceedings of the National Academy of Sciences of the United States of America 88 23650393
2018 The circular RNA circ-ITCH suppresses ovarian carcinoma progression through targeting miR-145/RASA1 signaling. Biochemical and biophysical research communications 85 30243714
2014 Degradation of connexins and gap junctions. FEBS letters 84 24486527
2005 Annexin A6 stimulates the membrane recruitment of p120GAP to modulate Ras and Raf-1 activity. Oncogene 84 15940262
2011 Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration. The Journal of cell biology 83 21768288
2004 Regulation of gap junctions by tyrosine protein kinases. Biochimica et biophysica acta 82 15033580
2012 Gap junction and hemichannel functions in osteocytes. Bone 81 23069374
1998 Regulation of gap junctions by protein phosphorylation. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 79 9698763
2016 RASA1 somatic mutation and variable expressivity in capillary malformation/arteriovenous malformation (CM/AVM) syndrome. American journal of medical genetics. Part A 78 26969842
2019 Chromosomics: Bridging the Gap between Genomes and Chromosomes. Genes 76 31434289
2005 Bridging the neural gap. Clinics in plastic surgery 74 16139631
2009 A novel association between RASA1 mutations and spinal arteriovenous anomalies. AJNR. American journal of neuroradiology 70 20007727
2017 Gap junctions, pannexins and pain. Neuroscience letters 69 28647288
2014 RASA1 functions in EPHB4 signaling pathway to suppress endothelial mTORC1 activity. The Journal of clinical investigation 68 24837431
2004 Aspergillus fumigatus rasA and rasB regulate the timing and morphology of asexual development. Fungal genetics and biology : FG & B 67 14732259
2019 CircAHNAK1 inhibits proliferation and metastasis of triple-negative breast cancer by modulating miR-421 and RASA1. Aging 66 31857500
2018 Cancer Connectors: Connexins, Gap Junctions, and Communication. Frontiers in oncology 66 30622930
2017 Somatic second hit mutation of RASA1 in vascular endothelial cells in capillary malformation-arteriovenous malformation. European journal of medical genetics 64 29024832
1996 The Ca2+-dependent lipid binding domain of P120GAP mediates protein-protein interactions with Ca2+-dependent membrane-binding proteins. Evidence for a direct interaction between annexin VI and P120GAP. The Journal of biological chemistry 64 8798684
2017 RASA1 regulates the function of lymphatic vessel valves in mice. The Journal of clinical investigation 62 28530642
2015 C/EBP-β-activated microRNA-223 promotes tumour growth through targeting RASA1 in human colorectal cancer. British journal of cancer 61 25867276
2011 Can gap junctions deliver? Biochimica et biophysica acta 61 21986484
2007 Ubiquitination of gap junction proteins. The Journal of membrane biology 61 17657522
2022 Neurofibromin and suppression of tumorigenesis: beyond the GAP. Oncogene 60 35066574
2014 Connexins, gap junctions and tissue invasion. FEBS letters 60 24457198
2018 Glycomics@ExPASy: Bridging the Gap. Molecular & cellular proteomics : MCP 58 30097532
2017 RASA1 and NF1 are Preferentially Co-Mutated and Define A Distinct Genetic Subset of Smoking-Associated Non-Small Cell Lung Carcinomas Sensitive to MEK Inhibition. Clinical cancer research : an official journal of the American Association for Cancer Research 58 29127119
2005 Involvement of gap junctional communication in secretion. Biochimica et biophysica acta 58 16359942
2001 Archaeal primase: bridging the gap between RNA and DNA polymerases. Current biology : CB 58 11301257
2019 RASA1 mosaic mutations in patients with capillary malformation-arteriovenous malformation. Journal of medical genetics 56 31300548
2018 Expanding the clinical and molecular findings in RASA1 capillary malformation-arteriovenous malformation. European journal of human genetics : EJHG 54 29891884
2014 Gap junction regulation by calmodulin. FEBS letters 54 24440348
2008 Aspergillus fumigatus RasA regulates asexual development and cell wall integrity. Eukaryotic cell 53 18606827
2019 RASA1-dependent cellular export of collagen IV controls blood and lymphatic vascular development. The Journal of clinical investigation 51 31185000
2017 Joint diseases: from connexins to gap junctions. Nature reviews. Rheumatology 51 29255213
2015 MiR-21/RASA1 axis affects malignancy of colon cancer cells via RAS pathways. World journal of gastroenterology 51 25663768
2012 Identification and immunolocalisation of melatonin MT(1) and MT(2) receptors in Rasa Aragonesa ram spermatozoa. Reproduction, fertility, and development 51 22935156
2010 Gap junctions in inherited human disease. Pflugers Archiv : European journal of physiology 50 20140684
2006 Molecular mechanisms involved in Ras inactivation: the annexin A6-p120GAP complex. BioEssays : news and reviews in molecular, cellular and developmental biology 50 17120209
2002 Gap junctions and tumour progression. Canadian journal of physiology and pharmacology 50 11934256
2020 Role of RASA1 in cancer: A review and update (Review). Oncology reports 47 33125148
2009 Inactivation of Ras by p120GAP via focal adhesion kinase dephosphorylation mediates RGMa-induced growth cone collapse. The Journal of neuroscience : the official journal of the Society for Neuroscience 44 19458235
2018 Inside the Endometrial Cell Signaling Subway: Mind the Gap(s). International journal of molecular sciences 43 30134622
2011 Role of gap junctions in epilepsy. Neuroscience bulletin 39 22108816
2016 Protein tyrosine phosphatase 1B dephosphorylates PITX1 and regulates p120RasGAP in hepatocellular carcinoma. Hepatology (Baltimore, Md.) 38 26840794
2001 RACK1, a protein kinase C scaffolding protein, interacts with the PH domain of p120GAP. Biochemical and biophysical research communications 36 11350068
1998 Role of gap junctions in lung neoplasia. Experimental lung research 35 9659581
2016 Keloid progression: a stiffness gap hypothesis. International wound journal 34 27995750
1998 Rapid recruitment of p120RasGAP and its associated protein, p190RhoGAP, to the cytoskeleton during integrin mediated cell-substrate interaction. Oncogene 33 9690509
1998 Sam68 association with p120GAP in CD4+ T cells is dependent on CD4 molecule expression. Journal of immunology (Baltimore, Md. : 1950) 33 9743338
2014 GAP-independent functions of DLC1 in metastasis. Cancer metastasis reviews 32 24338004
2014 Functional cross-talk between ras and rho pathways: a Ras-specific GTPase-activating protein (p120RasGAP) competitively inhibits the RhoGAP activity of deleted in liver cancer (DLC) tumor suppressor by masking the catalytic arginine finger. The Journal of biological chemistry 31 24443565
2014 Connexins, gap junctions and peripheral neuropathy. Neuroscience letters 31 25449862
2011 RASA1 analysis: clinical and molecular findings in a series of consecutive cases. European journal of medical genetics 31 22200646
2001 Diversity and molecular anatomy of gap junctions. Medical electron microscopy : official journal of the Clinical Electron Microscopy Society of Japan 30 11793189
2017 A Transposon-based Analysis Reveals RASA1 Is Involved in Triple-Negative Breast Cancer. Cancer research 29 28108518
2014 Communication-dependent mineralization of osteoblasts via gap junctions. Bone 29 24389413

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